Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we...Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we developed a biomimetic nanoplatform(PLGA-UA@MA)composed of poly(lactic-co-glycolic acid)(PLGA)nanoparticles encapsulating the natural antitumor agent ursolic acid(UA),further cloaked with homologous gastric cancer cell membranes doped with the immunoadjuvant monophosphoryl lipid A(MPLA).This engineered system synergistically combines tumor-specific targeting,immune modulation,and stimuliresponsive drug release,presenting a precision therapeutic strategy for gastric cancer.PLGA-UA@M-A exhibits selective homing to primary tumor sites,facilitated by membrane fusion-mediated enhanced cellular uptake.In vitro studies demonstrated potent inhibition of MFC gastric cancer cell proliferation,induction of apoptosis,and suppression of metastatic behavior,underscoring its enhanced antitumor efficacy.Moreover,the nanoplatform triggered immunogenic cell death(ICD),while MPLA acted as an immunostimulant to promote dendritic cell maturation and T-cell priming—effectively reprogramming the immunosuppressive TME.In vivo evaluations confirmed excellent tumor accumulation,robust antitumor activity,and negligible systemic toxicity,highlighting its favorable biosafety profile.Collectively,PLGA-UA@M-A represents a multifunctional biomimetic delivery system that integrates chemotherapy with immune activation,offering a promising therapeutic paradigm for gastric cancer treatment.展开更多
Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereo...Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).展开更多
Background:Neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ration(PLR)have been shown to contribute to tumour progression and response to therapy.Methods:We retrospectively counted NLR and PLR in 719 patients ...Background:Neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ration(PLR)have been shown to contribute to tumour progression and response to therapy.Methods:We retrospectively counted NLR and PLR in 719 patients with advanced malignancies receiving chemo-and/or immuno-therapy.Results:Both the pretreatment NLR and PLR were significantly elevated in patients with progressive disease than in those without progressive disease.Compared to low groups,the high NLR and PLR groups showed significantly worse event free survival.Conclusion:We propose that NLR and PLR are not only effective blood markers for predicting therapeutic responses to chemo-and/or immuno-therapy,but also useful in detecting survival in diverse malignancies.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies often lead to a poor prognosis.AIM To assess the safety and efficacy of transarterial chemoembolization(TACE)with donafenib and immune checkpoint inhibitors(ICIs)for unresectable HCC.METHODS We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI(tislelizumab or cedilimumab).Patients received oral donafenib daily for 2 weeks before TACE,followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle.The primary endpoints were objective response rate,disease control rate,and duration of response according to the modified RECIST criteria.The secondary endpoint was presence of treatment-related adverse events(TRAEs).RESULTS The median follow-up was 7.8 months(95%CI:5.0-11.8 months).The objective response rate was 60.0%(18/30),while the disease control rate was 93.3%.The median duration of response in confirmed responders was 6.6 months(95%CI:1.3-12.9 months).The median progression-free survival was 11.8 months(95%CI:8.3-15.4 months).More than half of the patients survived until the end of the study.Grade>3 TRAEs occurred in 40%of the patients with no grade 5 TRAEs reported.The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia,a dermatologic condition characterized by painful redness and swelling of the palms and soles,with an incidence of 56.7%.No ICI-related adverse effects were observed.CONCLUSION TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.展开更多
Background:No clear evidence exists regarding the relationship between the systemic immune-inflammation index(SII)and the efficacy of first-line chemotherapy combined with immunotherapy in patients with advanced non-s...Background:No clear evidence exists regarding the relationship between the systemic immune-inflammation index(SII)and the efficacy of first-line chemotherapy combined with immunotherapy in patients with advanced non-small cell lung cancer(NSCLC).This study aimed to establish the relationship between the SII and survival of patients with advanced NSCLC.Methods:This study included 123 patients with advanced NSCLC.The cutoff value of the SII was determined to be 1172 using ROC curve analysis.We evaluated the relationship between the SII and progression-free survival(PFS)and overall survival(OS)using the Cox regression model and Kaplan-Meier(KM)curve analysis.We stratified patients into multiple subgroups based on covariates such as age,sex,and smoking history.Subgroup analysis was used to evaluate the relationship between high SII,disease progression,and mortality risk.Results:Univariate analysis indicated that no significant difference existed between SII and PFS,but univariate analysis showed a significant association between SII and OS(hazard ratio[HR]=1.93,95% confidence interval[CI]=1.14-3.29,p=0.015).The fully adjusted Cox regression analysis also showed a significant correlation between the SII and OS after adjustment for covariables(HR=1.76,95%CI=1.02-3.02,p=0.041).In some subgroups,a high SII positively correlated with the risk of disease progression,and the relationship between a high SII and the risk of mortality was consistent in almost all subgroups.Conclusions:These results indicate that pretreatment SII may be an independent predictivemarker for patients with advanced NSCLC undergoing first-line chemotherapy combined with immunotherapy.However,large-scale prospective studies are required to confirm our results.展开更多
Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolv...Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.展开更多
BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy co...BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy combined with immunotherapy(NACI)for locally advanced gastric cancer(LAGC)remains unclear.AIM To investigate the prognostic and predictive value of NET density in LAGC patients undergoing NACI.METHODS We enrolled 31 LAGC patients treated with NACI.NET density was assessed through dual immunofluorescence staining of citrullinated histone H3 and myeloperoxidase in pretreatment biopsy and post-treatment surgical specimens.Patients were stratified into high and low pre-NACI NET groups based on median NET density.Pathological complete response(pCR)and overall response rates were evaluated in relation to NET density.Logistic regression analyses were performed to identify independent predictors of treatment outcomes.Dynamic changes in NET density during NACI were also analyzed.RESULTS Patients with low pre-NACI NET density demonstrated significantly higher rates of pCR(40%vs 6%,P=0.037)and overall response(53%vs 12%,P=0.023)compared to those with high NET density.Low pre-NACI NET density and higher programmed death protein ligand 1 expression were identified as independent protective factors for achieving pCR and better response rates.NACI increased NET density;however,this increase was primarily observed in non-pCR and nonresponder groups.Patients in the pCR and responder groups showed stable NET density before and after treatment.Higher post-NACI NET density was associated with poorer respond to NACI.High post-NACI NET density was associated with increased infiltration of immunosuppressive FOXP3+T regulatory cells(P=0.025)and CD68+macrophages(P=0.038).CONCLUSION Pre-NACI NET density serves as a prognostic and predictive biomarker for NACI efficacy in LAGC patients.Low pretreatment NET density is associated with favorable outcomes,while increased post-treatment NET density correlates with poorer response.Targeting NET formation may represent a novel therapeutic strategy to enhance NACI efficacy in LAGC.展开更多
BACKGROUND Immunotherapy is an approved treatment for metastatic rectal cancer in patients with defective mismatch repair(MMR).AIM To examine the clinical efficacy of neoadjuvant immunotherapy combined with radiothera...BACKGROUND Immunotherapy is an approved treatment for metastatic rectal cancer in patients with defective mismatch repair(MMR).AIM To examine the clinical efficacy of neoadjuvant immunotherapy combined with radiotherapy and chemotherapy for the treatment of locally advanced rectal cancer(LARC),with a focus on patients with proficient MMR(pMMR)and mic-rosatellite stability.METHODS Two researchers searched multiple databases for publications up to September 2024.All included publications examined neoadjuvant immunotherapy for LARC,and reported major pathological response(MPR),pathological complete response(pCR),clinical complete response(CCR),and rates of R0 resection and anus-pre-serving surgery.Meta-analysis,subgroup analysis,sensitivity analysis,and ana-lysis of publication bias were performed.RESULTS We included 15 publications(796 patients).The MPR,pCR,and CCR were sig-nificantly better in the group that received immunotherapy(all P<0.05),espe-cially for patients with pMMR.In addition,the rate of R0 resection and anus-preserving surgery were also significantly greater in the group that received neoadjuvant immunotherapy(both P<0.05).Hematological toxicity and abnormal liver function were the most common clinical adverse events above grade 3.Most patients successfully completed the immunotherapy treatment.The incidence of immune-related adverse reactions was 0%-13.5%,and the severities of these events were generally considered acceptable.CONCLUSION The addition of neoadjuvant immunotherapy improved the clinical remission rate of patients who had LARC with pMMR,and the treatment-related adverse reactions were generally acceptable.Neoadjuvant immunotherapy combined with radiotherapy and chemotherapy should be considered for patients with LARC.展开更多
BACKGROUND The treatment of gastric cancer remains highly challenging,particularly in cases of unresectable locally advanced or metastatic disease.Although chemotherapy and immunotherapy have shown some efficacy in su...BACKGROUND The treatment of gastric cancer remains highly challenging,particularly in cases of unresectable locally advanced or metastatic disease.Although chemotherapy and immunotherapy have shown some efficacy in such patients,significant limitations persist in extending survival and enhancing safety.To address these challenges,we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1(PD-1)inhibitor with chemotherapy,and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity,with the metastasis being notably large in size.The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry.Considering the patient's status,the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel(nab-paclitaxel),S-1,and oxaliplatin as a quadruple drug conversion therapy.After 4 cycles of conversion therapy,the patient's epigastric pain was significantly alleviated,his stool color normalized,the volume of the primary tumor and lymph node metastases was markedly reduced,and the tumor marker levels decreased to within the normal range.The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection,and postoperative pathological biopsy revealed a pathological complete response and R0 resection,after which the patient recovered to an excellent physical status.CONCLUSION To the best of our knowledge,this is the first reported case of unresectable locally advanced gastric adenocar-cinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen.This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
AIM: To investigate whether autologous dendritic cell (DC)-cytokine-induced killer (CIK) cell therapy is able to improve the therapeutic efficacy of chemotherapy in colon cancer.
Metastatic melanoma has long been considered to have a very poor prognosis and to be chemo-resistant. However, a subgroup of patients with metastatic melanoma presents remarkable responses to chemotherapeutic agents, ...Metastatic melanoma has long been considered to have a very poor prognosis and to be chemo-resistant. However, a subgroup of patients with metastatic melanoma presents remarkable responses to chemotherapeutic agents, even in the absence of a response to modern targeted therapies and immunotherapies; accordingly, determining predictive biomarkers of the response to chemotherapies for metastatic melanoma remains a priority to guide treatment in these patients. We report a case study of a patient with B-Raf proto-oncogene serine/threonine kinase-mutated metastatic melanoma harbouring many genetic mutations. The patient did not respond to prior targeted therapies or immunotherapies but experienced a dramatic objective radiological and clinical response to subsequent dacarbazine-based chemotherapy. In the era of targeted therapies and immunotherapies for metastatic melanoma, cytotoxic chemotherapies may still represent an interesting therapeutic weapon in a well-deined subgroup of patients presenting with speciic genetic and molecular features.展开更多
Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immu...Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.展开更多
AIM: To evaluate the therapeutic efficacy of systemic chemo-immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy ...AIM: To evaluate the therapeutic efficacy of systemic chemo-immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy (PIAF regimen), which consisted of dsplatin (20 mg/m2) intravenously daily for 4 consecutive day, doxorubicin (40 mg/m2) intravenously on day 1, 5-fluorouracil (400 mg/m2) intravenously daily for 4 consecutive day, and human recombinant a-interferon-2a (5 Mu/m2) subcutaneous injection daily for 4 consecutive day. The treatment was repeated every 3 wk, with a maximum of six cycles. RESULTS: A total of 90 cycles of PIAF treatment were administered, with a mean number of 3.9 cycles per patient. Eight patients received six cycles of treatment (group A), and the remaining 18 were subjected to two to five cycles (group B). There were 0 complete response, 4 partial responses, 9 static diseases and 13 progressive diseases, with a disease control rate of 50% (13/26). The 1-year survival rate was 24.3%, with a median survival time of 6.0 mo. Group A had a remarkably better survival as compared with group B, the 1- and 2-year survival rates were 62.5% vs 6.1% and 32.3% vs 0%, and a median survival time was 12.5 mo vs5.0 mo (P= 0.001). CONCLUSION: Systemic chemo-immunotherapy using PIAF regimen represented an effective treatment and could improve the survival rate and prolong the survival time in selected patients with advanced HCC.展开更多
Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Ther...Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC. The conventional chemotherapeutic agent utilized throughout the last four decades is 5-fluorouracil, notwithstanding its low efficiency as a single therapy. In contrast, combining 5-fluorouracil therapy with leucovorin and oxaliplatin or irinotecan increases its efficiency. However, these treatments have limited and temporary solutions and aggressive side effects. Additionally, most patients treated with these regimens develop drug resistance, which leads to disease progression. The immune response is considered a hallmark of cancer;thus, the use of new strategies and methodologies involving immune molecules, cells, and transcription factors has been suggested for CRC patients diagnosed in stages Ⅲ and Ⅳ. Despite the critical advances in immunotherapy, the development and impact of immune checkpoint inhibitors on CRC is still under investigation because less than 25% of CRC patients display an increased 5-year survival. The causes of CRC are diverse and include modifiable environmental factors(smoking, diet, obesity, and alcoholism), individual genetic mutations, and inflammation-associated bowel diseases. Due to these diverse causes, the solutions likely cannot be generalized. Interestingly, new strategies, such as single-cell multiomics, proteomics, genomics, flow cytometry, and massive sequencing for tumor microenvironment analysis, are beginning to clarify the way forward. Thus,the individual mechanisms involved in developing the CRC microenvironment, their causes, and their consequences need to be understood from a genetic and immunological perspective. This review highlighted the importance of altering the immune response in CRC. It focused on drugs that may modulate the immune response and show specific efficacy and contrasted with evidence that immunosuppression or the promotion of the immune response is the answer to generating effective treatments with combined chemotherapeutic drugs.展开更多
BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more effi...BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.展开更多
Objective： Professional antigen-presenting dendritic cells （DCs） and cytokine-induced killer （CIK） cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic...Objective： Professional antigen-presenting dendritic cells （DCs） and cytokine-induced killer （CIK） cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic re- sistance. To evaluate whether DC-CIK cell-based therapy improves the clinical efficacy of chemotherapy, we reviewed the literature on DC-CIK cells and meta-analyzed randomized controlled trials （RCTs）. Methods： We searched several databases and selected studies using predeflned criteria. RCTs that applied chemotherapy with and without DC-CIK cells separately in two groups were included. Odds ratio （OR） and mean difference （MD） were reported to measure the pooled effect. Results： Twelve reported RCTs （826 patients）, which were all performed on Chinese patients, were included. Combination therapy exhibited better data than chemotherapy： 1-year overall survival （OS） （OR=0.22, P〈0.01）, 2-year OS （OR=0.28, P〈0.01）, 3-year OS （OR=0.41, P〈0.01）, 1-year disease-free survival （DFS） （OR=0.16, P〈0.05）, 3-year DFS （OR=0.32, P〈0.01）, objective response rate （ORR） （OR=0.54, P〈0.01）, and disease control rate （DCR） （OR=0.46, P〈0.01）. Moreover, the levels of CD3＋ T-lymphocytes （MD=-11.65, P〈0.05） and CD4＋ T-lymphocytes （MD=-8.18, P〈0.01） of the combination group were higher. Conclusions： Immunotherapy of DC-CIK cells may enhance the efficacy of chemotherapy on solid cancer and induces no specific side effect. Further RCTs with no publishing bias should be designed to confirm the immunotherapeutic effects of DC-CIK cells.展开更多
Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative bre...Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.展开更多
BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver cancer.AIM ...BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver cancer.AIM To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver cancer.METHODS Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected.All patients underwent Gamma Knife®treatment combined with TACE and immunotherapy.The clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were recorded.RESULTS The last follow-up for this study was conducted on October 31,2023.Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths reported.CONCLUSION Gamma Knife®combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.展开更多
BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[de...BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[dendritic cell-cytokine-induced killer(DC-CIK)cell immunotherapy]on patients after CRC surgery and to explore the mediating variables.METHODS A total cohort of 121 patients who underwent CRC surgery between January 2019 and April 2022 were selected.The sample comprised a control group of 55 pa-tients who received the XELOX chemotherapy regimen and a research group of 66 patients who received XELOX+DC-CIK immunotherapy.We performed compa-rative analyses of the clinical and pathological data of the two groups,including efficacy(2-year disease-free survival[DFS]rate),the incidence of adverse events(diarrhea,myelosuppression,gastrointestinal reactions,and peripheral neuritis),serum levels of tumor markers[carcinoembryonic antigens and carbohydrate an-tigens(CA)19-9 and CA242],and T-cell subsets[cluster of differentiation(CD)3+,CD3+CD4+,CD3+CD8+,natural killer(NK),and NK T cells].We also conducted preliminary univariate and mul-tivariate analyses of the variables that affected the efficacy of the treatments.RESULTS We found a significantly higher 2-year DFS rate of treatment efficacy in the research group than in the control group,with a statistically lower incidence of adverse events.Both groups showed a reduction in serum tumor markers after treatment but there was no marked intergroup difference.After treatment,the various T-cell subgroup indicators in the control group were significantly lower than those in the research group.The indices of T-cell subsets in the research group showed no significant change from preoperative levels.Univariate analysis revealed a significant correlation between TNM staging,tumor differentiation,and the rates of nonresponse to treatment in CRC patients after surgery.Multivariate results indicated that the treatment approach significantly affected the efficacy of postoperative CRC treatment.CONCLUSION We concluded that XELOX+DC-CIK immunotherapy for postsurgical CRC patients offers reduced rates of treatment-induced adverse events,extended 2-year DFS,enhanced immunity,and increased physiological antitumor responses.展开更多
基金supported by the National Natural Science Foundation of China(No.82360498)Gansu Joint Scientific Research Fund Major Project(No.23JRRA1537)+5 种基金the 2025 Central-Guided Local Science and Technology Development Found(No.25ZYJA003)Gansu Provincial Health Industry Science and Technology Innovation Major Project(No.GSWSZD2024-01)Gansu Province Key Talent Project(No.2025RCXM067)2024 Gansu Provincial Hospital Special Fund of NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor(No.23GSSYA-10)the 2021 Central-Guided Local Science and Technology Development Found(No.ZYYDDFFZZJ-1)Zhejiang Provincial Natural Science Foundation of China(No.LTGY23H160032).
文摘Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we developed a biomimetic nanoplatform(PLGA-UA@MA)composed of poly(lactic-co-glycolic acid)(PLGA)nanoparticles encapsulating the natural antitumor agent ursolic acid(UA),further cloaked with homologous gastric cancer cell membranes doped with the immunoadjuvant monophosphoryl lipid A(MPLA).This engineered system synergistically combines tumor-specific targeting,immune modulation,and stimuliresponsive drug release,presenting a precision therapeutic strategy for gastric cancer.PLGA-UA@M-A exhibits selective homing to primary tumor sites,facilitated by membrane fusion-mediated enhanced cellular uptake.In vitro studies demonstrated potent inhibition of MFC gastric cancer cell proliferation,induction of apoptosis,and suppression of metastatic behavior,underscoring its enhanced antitumor efficacy.Moreover,the nanoplatform triggered immunogenic cell death(ICD),while MPLA acted as an immunostimulant to promote dendritic cell maturation and T-cell priming—effectively reprogramming the immunosuppressive TME.In vivo evaluations confirmed excellent tumor accumulation,robust antitumor activity,and negligible systemic toxicity,highlighting its favorable biosafety profile.Collectively,PLGA-UA@M-A represents a multifunctional biomimetic delivery system that integrates chemotherapy with immune activation,offering a promising therapeutic paradigm for gastric cancer treatment.
基金supported by the Shenzhen Science and Technology Program(grant number:KQTD20180411185028798).
文摘Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).
基金supported by the project of Young Technical Talents of Tianjin Medical University General Hospital(GG-2021-08).
文摘Background:Neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ration(PLR)have been shown to contribute to tumour progression and response to therapy.Methods:We retrospectively counted NLR and PLR in 719 patients with advanced malignancies receiving chemo-and/or immuno-therapy.Results:Both the pretreatment NLR and PLR were significantly elevated in patients with progressive disease than in those without progressive disease.Compared to low groups,the high NLR and PLR groups showed significantly worse event free survival.Conclusion:We propose that NLR and PLR are not only effective blood markers for predicting therapeutic responses to chemo-and/or immuno-therapy,but also useful in detecting survival in diverse malignancies.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options.This is particularly true for advanced HCC,for which conventional therapies often lead to a poor prognosis.AIM To assess the safety and efficacy of transarterial chemoembolization(TACE)with donafenib and immune checkpoint inhibitors(ICIs)for unresectable HCC.METHODS We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI(tislelizumab or cedilimumab).Patients received oral donafenib daily for 2 weeks before TACE,followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle.The primary endpoints were objective response rate,disease control rate,and duration of response according to the modified RECIST criteria.The secondary endpoint was presence of treatment-related adverse events(TRAEs).RESULTS The median follow-up was 7.8 months(95%CI:5.0-11.8 months).The objective response rate was 60.0%(18/30),while the disease control rate was 93.3%.The median duration of response in confirmed responders was 6.6 months(95%CI:1.3-12.9 months).The median progression-free survival was 11.8 months(95%CI:8.3-15.4 months).More than half of the patients survived until the end of the study.Grade>3 TRAEs occurred in 40%of the patients with no grade 5 TRAEs reported.The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia,a dermatologic condition characterized by painful redness and swelling of the palms and soles,with an incidence of 56.7%.No ICI-related adverse effects were observed.CONCLUSION TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.
基金supported by grants from the“Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation”under Grant No.2023JJA141341the“Guangxi Medical and Health Key Discipline Construction Project.”。
文摘Background:No clear evidence exists regarding the relationship between the systemic immune-inflammation index(SII)and the efficacy of first-line chemotherapy combined with immunotherapy in patients with advanced non-small cell lung cancer(NSCLC).This study aimed to establish the relationship between the SII and survival of patients with advanced NSCLC.Methods:This study included 123 patients with advanced NSCLC.The cutoff value of the SII was determined to be 1172 using ROC curve analysis.We evaluated the relationship between the SII and progression-free survival(PFS)and overall survival(OS)using the Cox regression model and Kaplan-Meier(KM)curve analysis.We stratified patients into multiple subgroups based on covariates such as age,sex,and smoking history.Subgroup analysis was used to evaluate the relationship between high SII,disease progression,and mortality risk.Results:Univariate analysis indicated that no significant difference existed between SII and PFS,but univariate analysis showed a significant association between SII and OS(hazard ratio[HR]=1.93,95% confidence interval[CI]=1.14-3.29,p=0.015).The fully adjusted Cox regression analysis also showed a significant correlation between the SII and OS after adjustment for covariables(HR=1.76,95%CI=1.02-3.02,p=0.041).In some subgroups,a high SII positively correlated with the risk of disease progression,and the relationship between a high SII and the risk of mortality was consistent in almost all subgroups.Conclusions:These results indicate that pretreatment SII may be an independent predictivemarker for patients with advanced NSCLC undergoing first-line chemotherapy combined with immunotherapy.However,large-scale prospective studies are required to confirm our results.
文摘Lung cancer is a common cause of cancer-related death globally.The majority of lung cancer patients initially benefit from chemotherapy and immunotherapy.However,as the treatment cycle progresses and the disease evolves,the emergence of acquired resistance leads to treatment failure.Many researches have shown that non-coding RNAs(ncRNAs)not only influence lung cancer progression but also act as potential mediators of immunotherapy and chemotherapy resistance in lung cancer,mediating drug resistance by regulating multiple targets and pathways.In addition,the regulation of immune response by ncRNAs is dualistic,forming a microenvironment for inhibits/promotes immune escape through changes in the expression of immune checkpoints.The aim of this review is to understand the effects of ncRNAs on the occurrence and development of lung cancer,focusing on the role of ncRNAs in regulating drug resistance of lung cancer.
文摘BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy combined with immunotherapy(NACI)for locally advanced gastric cancer(LAGC)remains unclear.AIM To investigate the prognostic and predictive value of NET density in LAGC patients undergoing NACI.METHODS We enrolled 31 LAGC patients treated with NACI.NET density was assessed through dual immunofluorescence staining of citrullinated histone H3 and myeloperoxidase in pretreatment biopsy and post-treatment surgical specimens.Patients were stratified into high and low pre-NACI NET groups based on median NET density.Pathological complete response(pCR)and overall response rates were evaluated in relation to NET density.Logistic regression analyses were performed to identify independent predictors of treatment outcomes.Dynamic changes in NET density during NACI were also analyzed.RESULTS Patients with low pre-NACI NET density demonstrated significantly higher rates of pCR(40%vs 6%,P=0.037)and overall response(53%vs 12%,P=0.023)compared to those with high NET density.Low pre-NACI NET density and higher programmed death protein ligand 1 expression were identified as independent protective factors for achieving pCR and better response rates.NACI increased NET density;however,this increase was primarily observed in non-pCR and nonresponder groups.Patients in the pCR and responder groups showed stable NET density before and after treatment.Higher post-NACI NET density was associated with poorer respond to NACI.High post-NACI NET density was associated with increased infiltration of immunosuppressive FOXP3+T regulatory cells(P=0.025)and CD68+macrophages(P=0.038).CONCLUSION Pre-NACI NET density serves as a prognostic and predictive biomarker for NACI efficacy in LAGC patients.Low pretreatment NET density is associated with favorable outcomes,while increased post-treatment NET density correlates with poorer response.Targeting NET formation may represent a novel therapeutic strategy to enhance NACI efficacy in LAGC.
基金Supported by Start-up Fund for Doctor's Scientific Research in Shanxi Cancer Hospital,No.Dr202314and Natural Exploration Category of Shanxi Basic Research Plan,No.202203021221284.
文摘BACKGROUND Immunotherapy is an approved treatment for metastatic rectal cancer in patients with defective mismatch repair(MMR).AIM To examine the clinical efficacy of neoadjuvant immunotherapy combined with radiotherapy and chemotherapy for the treatment of locally advanced rectal cancer(LARC),with a focus on patients with proficient MMR(pMMR)and mic-rosatellite stability.METHODS Two researchers searched multiple databases for publications up to September 2024.All included publications examined neoadjuvant immunotherapy for LARC,and reported major pathological response(MPR),pathological complete response(pCR),clinical complete response(CCR),and rates of R0 resection and anus-pre-serving surgery.Meta-analysis,subgroup analysis,sensitivity analysis,and ana-lysis of publication bias were performed.RESULTS We included 15 publications(796 patients).The MPR,pCR,and CCR were sig-nificantly better in the group that received immunotherapy(all P<0.05),espe-cially for patients with pMMR.In addition,the rate of R0 resection and anus-preserving surgery were also significantly greater in the group that received neoadjuvant immunotherapy(both P<0.05).Hematological toxicity and abnormal liver function were the most common clinical adverse events above grade 3.Most patients successfully completed the immunotherapy treatment.The incidence of immune-related adverse reactions was 0%-13.5%,and the severities of these events were generally considered acceptable.CONCLUSION The addition of neoadjuvant immunotherapy improved the clinical remission rate of patients who had LARC with pMMR,and the treatment-related adverse reactions were generally acceptable.Neoadjuvant immunotherapy combined with radiotherapy and chemotherapy should be considered for patients with LARC.
基金Supported by the Health Industry Research Program of Gansu Province,No.GSWSKY2021-043the Youth Science and Technology Foundation of Gansu Province,No.22JR11RA002the Natural Science Foundation of Gansu Province,No.22JR5RA008.
文摘BACKGROUND The treatment of gastric cancer remains highly challenging,particularly in cases of unresectable locally advanced or metastatic disease.Although chemotherapy and immunotherapy have shown some efficacy in such patients,significant limitations persist in extending survival and enhancing safety.To address these challenges,we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1(PD-1)inhibitor with chemotherapy,and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity,with the metastasis being notably large in size.The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry.Considering the patient's status,the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel(nab-paclitaxel),S-1,and oxaliplatin as a quadruple drug conversion therapy.After 4 cycles of conversion therapy,the patient's epigastric pain was significantly alleviated,his stool color normalized,the volume of the primary tumor and lymph node metastases was markedly reduced,and the tumor marker levels decreased to within the normal range.The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection,and postoperative pathological biopsy revealed a pathological complete response and R0 resection,after which the patient recovered to an excellent physical status.CONCLUSION To the best of our knowledge,this is the first reported case of unresectable locally advanced gastric adenocar-cinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen.This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
基金Supported by National Natural Science Foundation of China,No.31171427 and No.30971651 to Wang ZXNational Natural Science Foundation of China,No.30700974 to Cao JXPostdoctoral Foundation of China,No.20060400775 to Cao JX
文摘AIM: To investigate whether autologous dendritic cell (DC)-cytokine-induced killer (CIK) cell therapy is able to improve the therapeutic efficacy of chemotherapy in colon cancer.
文摘Metastatic melanoma has long been considered to have a very poor prognosis and to be chemo-resistant. However, a subgroup of patients with metastatic melanoma presents remarkable responses to chemotherapeutic agents, even in the absence of a response to modern targeted therapies and immunotherapies; accordingly, determining predictive biomarkers of the response to chemotherapies for metastatic melanoma remains a priority to guide treatment in these patients. We report a case study of a patient with B-Raf proto-oncogene serine/threonine kinase-mutated metastatic melanoma harbouring many genetic mutations. The patient did not respond to prior targeted therapies or immunotherapies but experienced a dramatic objective radiological and clinical response to subsequent dacarbazine-based chemotherapy. In the era of targeted therapies and immunotherapies for metastatic melanoma, cytotoxic chemotherapies may still represent an interesting therapeutic weapon in a well-deined subgroup of patients presenting with speciic genetic and molecular features.
基金supported by the National Natural Science Foundation of China(No.81974498,No.81773652)。
文摘Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.
文摘AIM: To evaluate the therapeutic efficacy of systemic chemo-immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy (PIAF regimen), which consisted of dsplatin (20 mg/m2) intravenously daily for 4 consecutive day, doxorubicin (40 mg/m2) intravenously on day 1, 5-fluorouracil (400 mg/m2) intravenously daily for 4 consecutive day, and human recombinant a-interferon-2a (5 Mu/m2) subcutaneous injection daily for 4 consecutive day. The treatment was repeated every 3 wk, with a maximum of six cycles. RESULTS: A total of 90 cycles of PIAF treatment were administered, with a mean number of 3.9 cycles per patient. Eight patients received six cycles of treatment (group A), and the remaining 18 were subjected to two to five cycles (group B). There were 0 complete response, 4 partial responses, 9 static diseases and 13 progressive diseases, with a disease control rate of 50% (13/26). The 1-year survival rate was 24.3%, with a median survival time of 6.0 mo. Group A had a remarkably better survival as compared with group B, the 1- and 2-year survival rates were 62.5% vs 6.1% and 32.3% vs 0%, and a median survival time was 12.5 mo vs5.0 mo (P= 0.001). CONCLUSION: Systemic chemo-immunotherapy using PIAF regimen represented an effective treatment and could improve the survival rate and prolong the survival time in selected patients with advanced HCC.
文摘Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC. The conventional chemotherapeutic agent utilized throughout the last four decades is 5-fluorouracil, notwithstanding its low efficiency as a single therapy. In contrast, combining 5-fluorouracil therapy with leucovorin and oxaliplatin or irinotecan increases its efficiency. However, these treatments have limited and temporary solutions and aggressive side effects. Additionally, most patients treated with these regimens develop drug resistance, which leads to disease progression. The immune response is considered a hallmark of cancer;thus, the use of new strategies and methodologies involving immune molecules, cells, and transcription factors has been suggested for CRC patients diagnosed in stages Ⅲ and Ⅳ. Despite the critical advances in immunotherapy, the development and impact of immune checkpoint inhibitors on CRC is still under investigation because less than 25% of CRC patients display an increased 5-year survival. The causes of CRC are diverse and include modifiable environmental factors(smoking, diet, obesity, and alcoholism), individual genetic mutations, and inflammation-associated bowel diseases. Due to these diverse causes, the solutions likely cannot be generalized. Interestingly, new strategies, such as single-cell multiomics, proteomics, genomics, flow cytometry, and massive sequencing for tumor microenvironment analysis, are beginning to clarify the way forward. Thus,the individual mechanisms involved in developing the CRC microenvironment, their causes, and their consequences need to be understood from a genetic and immunological perspective. This review highlighted the importance of altering the immune response in CRC. It focused on drugs that may modulate the immune response and show specific efficacy and contrasted with evidence that immunosuppression or the promotion of the immune response is the answer to generating effective treatments with combined chemotherapeutic drugs.
基金This study was reviewed and approved by the Ethics Committee of Zhongshan People’s Hospital(Approval No.2022-029).
文摘BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.
基金supported by the Medical and Health Technology Development Project of Shandong Province,China(No.2014WS0351)
文摘Objective： Professional antigen-presenting dendritic cells （DCs） and cytokine-induced killer （CIK） cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic re- sistance. To evaluate whether DC-CIK cell-based therapy improves the clinical efficacy of chemotherapy, we reviewed the literature on DC-CIK cells and meta-analyzed randomized controlled trials （RCTs）. Methods： We searched several databases and selected studies using predeflned criteria. RCTs that applied chemotherapy with and without DC-CIK cells separately in two groups were included. Odds ratio （OR） and mean difference （MD） were reported to measure the pooled effect. Results： Twelve reported RCTs （826 patients）, which were all performed on Chinese patients, were included. Combination therapy exhibited better data than chemotherapy： 1-year overall survival （OS） （OR=0.22, P〈0.01）, 2-year OS （OR=0.28, P〈0.01）, 3-year OS （OR=0.41, P〈0.01）, 1-year disease-free survival （DFS） （OR=0.16, P〈0.05）, 3-year DFS （OR=0.32, P〈0.01）, objective response rate （ORR） （OR=0.54, P〈0.01）, and disease control rate （DCR） （OR=0.46, P〈0.01）. Moreover, the levels of CD3＋ T-lymphocytes （MD=-11.65, P〈0.05） and CD4＋ T-lymphocytes （MD=-8.18, P〈0.01） of the combination group were higher. Conclusions： Immunotherapy of DC-CIK cells may enhance the efficacy of chemotherapy on solid cancer and induces no specific side effect. Further RCTs with no publishing bias should be designed to confirm the immunotherapeutic effects of DC-CIK cells.
基金the projects of the National Key Research and Development Program(No.2021YFA0716702)the National Natural Science Foundation of China(Nos.61805122,22022404 and 22074050)+5 种基金Green Industry Science and Technology Leading Project of Hubei University of Technology(No.XJ2021003301)the National Natural Science Foundation of Hubei Province(No.2022CFA033)supported by Chinese Society of Clinical Oncology(CSCO)supported by Jiangsu Hengrui Cancer Research Foundation(No.YHR2019–0325)supported by the Fundamental Research Funds for the Central Universities(No.CCNU22QN007)supported by the Opening Fund from the Jiangsu Key Laboratory of Medical Optics,Suzhou Institute of Biomedical Engineering and Technology(No.JKLMO202203)supported by the Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science,MO(No.M2022–5).
文摘Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.
文摘BACKGROUND This study was designed to investigate the clinical efficacy and safety of Gamma Knife®combined with transarterial chemoembolization(TACE)and immunotherapy in the treatment of primary liver cancer.AIM To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver cancer.METHODS Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected.All patients underwent Gamma Knife®treatment combined with TACE and immunotherapy.The clinical efficacy,changes in liver function,overall survival(OS),and progression-free survival(PFS)of patients with different treatment responses were evaluated,and adverse reactions were recorded.RESULTS The last follow-up for this study was conducted on October 31,2023.Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response(PR)in 27 patients,accounting for 52.94%(27/51);stable disease(SD)in 16 patients,accounting for 31.37%(16/51);and progressive disease(PD)in 8 patients,accounting for 15.69%(8/51).The objective response rate was 52.94%,and the disease control rate was 84.31%.Alanine aminotransferase,aspartate aminotransferase,lactate dehydrogenase,and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment(all P=0.000).The median OS was 26 months[95%confidence interval(95%CI):19.946-32.054]in the PR group and 19 months(95%CI:14.156-23.125)in the SD+PD group,with a statistically significant difference(P=0.015).The median PFS was 20 months(95%CI:18.441-34.559)in the PR group and 12 months(95%CI:8.745-13.425)in the SD+PD group,with a statistically significant difference(P=0.002).Common adverse reactions during treatment included nausea and vomiting(39.22%),thrombocytopenia(27.45%),and leukopenia(25.49%),with no treatment-related deaths reported.CONCLUSION Gamma Knife®combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.
文摘BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[dendritic cell-cytokine-induced killer(DC-CIK)cell immunotherapy]on patients after CRC surgery and to explore the mediating variables.METHODS A total cohort of 121 patients who underwent CRC surgery between January 2019 and April 2022 were selected.The sample comprised a control group of 55 pa-tients who received the XELOX chemotherapy regimen and a research group of 66 patients who received XELOX+DC-CIK immunotherapy.We performed compa-rative analyses of the clinical and pathological data of the two groups,including efficacy(2-year disease-free survival[DFS]rate),the incidence of adverse events(diarrhea,myelosuppression,gastrointestinal reactions,and peripheral neuritis),serum levels of tumor markers[carcinoembryonic antigens and carbohydrate an-tigens(CA)19-9 and CA242],and T-cell subsets[cluster of differentiation(CD)3+,CD3+CD4+,CD3+CD8+,natural killer(NK),and NK T cells].We also conducted preliminary univariate and mul-tivariate analyses of the variables that affected the efficacy of the treatments.RESULTS We found a significantly higher 2-year DFS rate of treatment efficacy in the research group than in the control group,with a statistically lower incidence of adverse events.Both groups showed a reduction in serum tumor markers after treatment but there was no marked intergroup difference.After treatment,the various T-cell subgroup indicators in the control group were significantly lower than those in the research group.The indices of T-cell subsets in the research group showed no significant change from preoperative levels.Univariate analysis revealed a significant correlation between TNM staging,tumor differentiation,and the rates of nonresponse to treatment in CRC patients after surgery.Multivariate results indicated that the treatment approach significantly affected the efficacy of postoperative CRC treatment.CONCLUSION We concluded that XELOX+DC-CIK immunotherapy for postsurgical CRC patients offers reduced rates of treatment-induced adverse events,extended 2-year DFS,enhanced immunity,and increased physiological antitumor responses.
