Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—com...Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—comprised of interacting endothelial,stromal,and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and,thus,the establishment of metastases.The liver’s intrinsic nature further facilitates the development of immune tolerance,mediated by regulatory T cells,myeloid-derived suppressor cells,and soluble factors such as anti-inflammatory cytokines,which together dampen antitumor immune responses.This immunosuppressive milieu contributes significantly to resistance to immune checkpoint inhibitors,limiting the efficacy of immunotherapy in metastatic CRC.Deciphering the complex crosstalk between metastatic CRC cells and TME within the liver is essential for developing novel,effective immunotherapeutic approaches.Several strategies to overcome this lack of response are under research,including combination therapies,novel compounds,and approaches that target TME components.The scope of this review is to synthesize recent advances in the characterization of the hepatic metastatic microenvironment and emerging therapeutic approaches aimed at overcoming immune resistance in CRC liver metastases.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
Skin cancer remains the most commonly diagnosed malignancy worldwide,with basal cell carcinoma(BCC),cutaneous squamous cell carcinoma(cSCC),and melanoma representing the most clinically significant types.While traditi...Skin cancer remains the most commonly diagnosed malignancy worldwide,with basal cell carcinoma(BCC),cutaneous squamous cell carcinoma(cSCC),and melanoma representing the most clinically significant types.While traditional treatments are effective for early-stage disease,advanced or metastatic cases often pose significant therapeutic challenges.Patients with high-risk or recurrent disease face limited options and poor prognoses.The emergence of immunotherapy has dramatically transformed the treatment landscape across multiple cancer types,including cutaneous malignancies.This review highlights recent advancements in immunotherapeutic strategies for BCC,cSCC,and melanoma,underscoring their growing importance in dermatologic oncology.We synthesize current evidence and ongoing clinical trials for immunotherapy across these three skin cancer types.We also explore the molecular mechanisms underpinning immune responsiveness and potential biomarkers of response.As immunotherapy continues to expand within dermatology,understanding its role,limitations,and future directions is essential for optimizing patient care.The integration of immunotherapy into dermatologic practice represents not only a therapeutic innovation but also a shift toward precision medicine in cutaneous oncology.展开更多
Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immuno...Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop met...Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.展开更多
Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune check...Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.展开更多
Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving resear...Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironm...Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.展开更多
Objective:To analyze the efficacy of allergen subcutaneous injection immunotherapy in patients with allergic rhinitis.Methods:Fifty patients with allergic rhinitis admitted from May 2023 to May 2025 were selected as s...Objective:To analyze the efficacy of allergen subcutaneous injection immunotherapy in patients with allergic rhinitis.Methods:Fifty patients with allergic rhinitis admitted from May 2023 to May 2025 were selected as study subjects and randomly divided into a control group and an observation group,with 25 patients in each group.The control group was treated with budesonide nasal spray,while the observation group received allergen subcutaneous injection immunotherapy in addition to the control treatment.The treatment efficacy,adverse reactions,symptom improvement time,and immune indicators were compared between the two groups.Results:The observation group showed a higher disease treatment efficacy than the control group(p<0.05);the incidence of adverse reactions in the observation group was not statistically significant compared to the control group(p>0.05);the observation group had a shorter symptom improvement time for nasal obstruction,rhinorrhea,and sneezing than the control group(p<0.05);before treatment,there was no statistical significance in immune indicators between the two groups(p>0.05);after treatment,CD3+and CD4/CD8+in the observation group were higher than those in the control group(p<0.05).Conclusion:Allergen subcutaneous injection immunotherapy in patients with allergic rhinitis can improve disease treatment efficacy,alleviate clinical symptoms,and enhance immune function.This therapy is safe and has clinical application value.展开更多
The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was domin...The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was dominated by surgery,chemotherapy,radiotherapy,and targeted therapies1.However,the advent of immune checkpoint inhibitors(ICIs)has challenged this paradigm,opening a new frontier.The initial breakthrough in triple-negative breast cancer(TNBC)demonstrated that a subset of patients could derive profound and durable clinical benefit from pembrolizumab and atezolizumab2,3.Today,precision immunotherapy aims to identify the patients most likely to respond,to convert immunologically silent tumors into responsive tumors,and to strategically combine immunotherapies with other modalities to overcome resistance.This evolution from empirical application to biomarker-driven strategies marks the critical juncture at which we stand,transitioning promising clinical trial data into refined,effective,and accessible clinical practice4.Recent key clinical studies on breast cancer immunotherapy are summarized in Table 1.展开更多
Background:Thimerosal is a mercury-containing preservative widely used in vaccines.This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies,particularly colorectal cancer(CR...Background:Thimerosal is a mercury-containing preservative widely used in vaccines.This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies,particularly colorectal cancer(CRC)and melanoma.Methods:A combination of in vitro and in vivo approaches was employed.Cell proliferation,apoptosis,migration,and invasion were assessed using Cell Counting Kit-8(CCK-8),colony formation,ATP viability,Western blotting,flow cytometry,wound-healing and Transwell assays.Subcutaneous,lung metastases,and Azoxymethane/Dextran Sulfate Sodium Salt(AOM/DSS)-induced colitis-associated CRC models were established to examine antitumor efficacy and safety.The functional role of mercury ions was validated using structural analogues.Mechanistic studies included RNA sequencing,Western blot,and immunohistochemical analysis of CD8^(+)T cell infiltration.The synergistic effect with programmed cell death protein 1(PD-1)antibody therapy was also evaluated.Results:Thimerosal potently inhibited tumor growth(with IC_(50) values ranging from 0.1 to 1μM in vitro)and significantly prolonged survival without overt toxicity in vivo.Mechanistically,mercury ions were identified as critical functional sites mediating Thimerosal’s antitumor effects.Specifically,Thimerosal inhibited the phosphorylation of Janus kinase 1(JAK1)and signal transducer and activator of transcription 3(STAT3).Furthermore,it enhanced the infiltration of CD8^(+)T cells into the tumor microenvironment and synergistically augmented the efficacy of anti-PD-1 therapy.Conclusion:Thimerosal exerts dual antitumor roles by direct JAK1/STAT3 inhibition and immune modulation via CD8^(+)T cell recruitment.It represents a promising repurposed drug and immunotherapeutic adjuvant for CRC and melanoma.展开更多
Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global hea...Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.展开更多
Objective:Immune checkpoint inhibitors(ICIs)have demonstrated substantial efficacy in patients with advanced non-small cell lung cancer(NSCLC).However,the optimal duration of ICI therapy remains unclear,and limited re...Objective:Immune checkpoint inhibitors(ICIs)have demonstrated substantial efficacy in patients with advanced non-small cell lung cancer(NSCLC).However,the optimal duration of ICI therapy remains unclear,and limited real-world data are available.The aim of this study was to evaluate the relationship between ICI therapy duration and overall survival(OS)in patients who achieved varying best overall response(BOR)during ICI treatment,and to compare patients treated for 6 to 18 months vs.at least 18 months.Methods:This retrospective cohort study included adult patients diagnosed with advanced NSCLC who received ICI therapy at the Zhejiang Cancer Hospital between 2017 and 2022.Data collection ended on May 1,2024,and statistical analysis was performed between May and June 2024.Results:Using strict entry criteria,we screened 487 patients with advanced NSCLC and identified 134 eligible patients.Among these patients,the median durations of immunotherapy and follow-up were 24.57 months and 43.60 months,respectively.The objective response rate(ORR)was 58.2%,and the median progression-free survival(PFS)was 10.6 months.Median OS was not reached.At the last follow-up,54 patients had no disease progression,and 118 patients remained alive.Patients treated with ICI therapy for≥18 months had superior survival to those treated for 6 to 18 months(P=0.039).Further analysis revealed that the survival benefit was associated with BOR during ICI therapy.Specifically,patients achieving complete response/partial response(CR/PR)who received≥18 months of ICI therapy had a trend toward longer median OS than those treated for 6 to 18 months,but the difference did not reach statistical significance(P=0.177).Patients with stable disease(SD)who received≥18 months of ICI therapy had a statistically longer median OS than those treated for 6 to 18 months(P=0.019).Among patients treated with ICIs for≥18 months,24 continued with ICI-based therapy and achieved a median PFS2 of 6.67 months,an ORR of 33.3%,and a disease control rate(DCR)of 83.3%.Conclusions:This study provides real-world evidence and novel insights into the need for continuing ICI therapy beyond 18 months in patients with advanced NSCLC who do not exhibit progressive disease.For patients achieving SD during ICI therapy,a treatment duration of at least 18 months appears appropriate.For patients achieving CR/PR,treatment decisions should be individualized according to patient-specific circumstances.However,owing to the retrospective study design,potential selection bias and confounding factors might have influenced the results.Therefore,our findings require further validation in prospective clinical studies.展开更多
Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC case...Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC cases.Despite advancements in targeted therapies and localized treatments,the 5-year survival rate remains low,indicating limited efficacy of current approaches.The advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has brought new hope for patients with PLC.However,the liver's unique immune microenvironment presents significant challenges to the effectiveness of immunotherapy in HCC.This article reviews recent research developments in liver cancer immunotherapy,focusing on ICIs,combination therapies,emerging treatments,and prospective future directions.展开更多
Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells,reducing the overall tumor burden.Increasing evidence suggests that conventional therapies possess sign...Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells,reducing the overall tumor burden.Increasing evidence suggests that conventional therapies possess significant immunomodulatory properties in addition to their established direct tumoricidal effects.Emerging immunotherapies have revolutionized the clinical management of various cancer types.Conventional therapy and immunotherapy have demonstrated remarkable clinical efficacy,leading to numerous ongoing clinical investiga-tions exploring their potential synergistic effects.However,trials investigating the combination of conventional therapy and immunotherapy have shown limited synergistic therapeutic efficacy.This unsatisfactory clinical outcome may be attributed to the suboptimal design of the combination approach and the inadequate understanding of the mechanisms and impacts of radiotherapy,chemotherapy,targeted ther-apy regimens(including dosing,timing,and administration route),and surgery on both cancer cells and the host immune system.Here,we comprehensively review preclinical and clinical investigations exploring the therapeutic effects and mechanisms of conventional therapy alone or in combination with immunotherapy.We proposed that optimizing the dosing,timing,and route of administration of conventional therapies can enhance the synergistic efficacy of combination therapies,thus offering significant clinical advantages.展开更多
Allergen specific immunotherapy(AIT)has a history spanning over 110 years and represents the only diseasemodifying treatment for allergic diseases,with potential preventive effects.Nevertheless,the broader application...Allergen specific immunotherapy(AIT)has a history spanning over 110 years and represents the only diseasemodifying treatment for allergic diseases,with potential preventive effects.Nevertheless,the broader application of AIT is limited by the inherent drawbacks of natural allergen extracts,such as variability in composition,risk of side effects,and complex,lengthy treatment regimens.Advances in molecular allergology have enabled the development of novel vaccine strategies-including recombinant allergens,hypoallergenic derivatives,allergen-derived peptides,and nucleic acid-based vaccines-that aim to improve safety,efficacy,and precision.However,no molecule-based AIT product has yet achieved regulatory approval,largely due to technical and clinical trial challenges.In parallel,immunomodulatory adjuvants such as monophosphoryl lipid A,CpG oligodeoxynucleotides,flagellin and mannan have demonstrated promising properties.These innovations have the potential to enhance AIT outcomes by promoting immune tolerance,reducing IgE responses,and improving patient compliance.This review summarizes the current landscape of allergen vaccines and adjuvant technologies under investigation for AIT,highlighting key advances,clinical data,and future directions aimed at overcoming existing limitations and optimizing treatment strategies for allergic diseases.展开更多
Cancer is a major global concern due to its high mortality rate.Tumor immunotherapy has revolutionized cancer treatment.However,low response rates and immune-related complications remain challenges.Extracellular vesic...Cancer is a major global concern due to its high mortality rate.Tumor immunotherapy has revolutionized cancer treatment.However,low response rates and immune-related complications remain challenges.Extracellular vesicles(EVs),including exosomes,have emerged as promising therapeutic tools for various pathological conditions,especially cancer.Evidence indicates that changes in the quantity and composition of EVs can influence the immunosuppressive tumor microenvironment,potentially affecting the effectiveness of immunotherapy.Exploiting EVs for immune sensitization has generated significant clinical interest.This review provides an in-depth understanding of the origin of EVs,their therapeutic applications(such as drug delivery nanoplatforms and cancer immunotherapies,including vaccines),diagnostic potential as tumor biomarkers,ongoing EV-based clinical trials,and the challenges encountered in EV-based cancer immunotherapy.展开更多
BACKGROUND Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer(GC).A comprehensive review of advancements,current status,and research trends in GC immunotherapy is essential to inform fut...BACKGROUND Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer(GC).A comprehensive review of advancements,current status,and research trends in GC immunotherapy is essential to inform future investigative efforts.AIM To delineate the trends,advancements,and focal points in immunotherapy for GC.METHODS We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20,2023,indexed in the Web of Science Core Collection.Data analysis and visualization were facilitated by CiteSpace(6.1.6R),VOSviewer v.1.6.17,and GraphPad Prism v8.0.2.RESULTS There has been an increase in the annual publication rate of GC immunotherapy research.China leads in publication volume,while the United States demonstrates the highest citation impact.Fudan University is notable for its citation frequency and publication output.Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis,the tumor microenvironment(TME),and integrative immunotherapy with targeted therapy.Emerging research areas include gastroesophageal junction cancer,adoptive immunotherapy,and the role of Treg cell in immunotherapy.CONCLUSION GC immunotherapy research is an expanding field attracting considerable scientific interest.With the clinical adoption of immunotherapy in GC,the primary goals are to enhance treatment efficacy and patient outcomes.Unlike hematological malignancies,GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells.For instance,although CAR-T therapy is effective in hematological malignancies,it has underperformed in GC settings.Current research is centered on overcoming immunosuppression within the TME,with a focus on combinations of targeted therapy,adoptive immunotherapy,Treg cell dynamics,and precise prognosis prediction in immunotherapy.Additionally,immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.展开更多
基金funded by the Italian Ministry of Health through the grant“PRIN 2022 PNRR”entitled“Landscape ANalyses of immune CEll signatures associated with early Liver metastatic cOlorecTal cancer”(LANCELOT),P2022N3NC4,which has received funding from European Commission—NextGeneration for the salary of the researcher Candela Cives-Losada.
文摘Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—comprised of interacting endothelial,stromal,and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and,thus,the establishment of metastases.The liver’s intrinsic nature further facilitates the development of immune tolerance,mediated by regulatory T cells,myeloid-derived suppressor cells,and soluble factors such as anti-inflammatory cytokines,which together dampen antitumor immune responses.This immunosuppressive milieu contributes significantly to resistance to immune checkpoint inhibitors,limiting the efficacy of immunotherapy in metastatic CRC.Deciphering the complex crosstalk between metastatic CRC cells and TME within the liver is essential for developing novel,effective immunotherapeutic approaches.Several strategies to overcome this lack of response are under research,including combination therapies,novel compounds,and approaches that target TME components.The scope of this review is to synthesize recent advances in the characterization of the hepatic metastatic microenvironment and emerging therapeutic approaches aimed at overcoming immune resistance in CRC liver metastases.
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.
文摘Skin cancer remains the most commonly diagnosed malignancy worldwide,with basal cell carcinoma(BCC),cutaneous squamous cell carcinoma(cSCC),and melanoma representing the most clinically significant types.While traditional treatments are effective for early-stage disease,advanced or metastatic cases often pose significant therapeutic challenges.Patients with high-risk or recurrent disease face limited options and poor prognoses.The emergence of immunotherapy has dramatically transformed the treatment landscape across multiple cancer types,including cutaneous malignancies.This review highlights recent advancements in immunotherapeutic strategies for BCC,cSCC,and melanoma,underscoring their growing importance in dermatologic oncology.We synthesize current evidence and ongoing clinical trials for immunotherapy across these three skin cancer types.We also explore the molecular mechanisms underpinning immune responsiveness and potential biomarkers of response.As immunotherapy continues to expand within dermatology,understanding its role,limitations,and future directions is essential for optimizing patient care.The integration of immunotherapy into dermatologic practice represents not only a therapeutic innovation but also a shift toward precision medicine in cutaneous oncology.
文摘Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis.Dynamic,bidirectional signaling between neural circuits and immune cells promotes tumor progression,shapes an immunosuppressive microenvironment,and contributes to therapeutic resistance.We synthesize current knowledge on how autonomic(sympathetic and parasympathetic)and sensory innervation regulate gastric cancer biology.These circuits act through neurotransmitters(catecholamines,acetylcholine)and neuropeptides(substance P[SP],calcitonin gene-related peptide[CGRP])to foster tumor growth and angiogenesis,facilitate perineural invasion,and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression.We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites.In parallel,we discuss why current immunotherapies achieve only modest response rates(approximately 10%-20%)in many settings,emphasizing neurally mediated mechanisms of resistance.We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation,selective neural ablation,and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation.This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
文摘Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.
基金supported by the National Natural Science Foundation of China(82472842 and 82473350)and Wuxi Double-Hundred Talent Fund Project(BJ2023075).
文摘Immunotherapy has brought unprecedented breakthroughs to advanced malignant tumors,yet the immune microenvironment shaped by the tumor stroma has often been underestimated in the traditional focus on the“immune checkpoint-T cell”axis.Collagen not only constitutes a mechanical barrier that distinguishes between the periphery and core of solid tumors but also systematically remodels the orientation of metabolism,vasculature,and immune cell phenotypic plasticity through its spatial density,fiber arrangement,and crosslinking patterns(F igure 1)[1,2].Abundant evidence suggests that over-accumulated types I and III collagen drive CD8+T cell exhaustion,NK cell functional inhibition,and tumor-associated macrophage polarization through ligand-receptor networks involving LAIR-1,DDR2,andβ1/β3 integrins[3-6].Mechanistically,collagen engagement of LAIR-1 delivers inhibitory signals in effector lymphocytes,promoting dysfunctional or exhausted states[7-9].In parallel,collagen-β1/β3 integrin signaling activates mechanotransduction pathways(e.g.,FAK/SRC),reducing T-cell motility and immune-tumor contact,while DDR2 activation supports matrix-remodeling programs that limit lymphocyte trafficking.
基金supported by Key Research and Development Plan of Hunan Province(2024DK2006)the Fundamental Research Funds for the Central Universities of Central South University(1053320221769)+2 种基金Hunan Provincial Respiratory Disease Rehabilitation and Nursing Engineering Research Center Innovation Capacity Building Project(No.202012)the Zhangjiajie Science and Technology Development Key Special Project(No.202304)the National Key Clinical Specialty Major Scientific Research Project(No.20230382).
文摘Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
基金supported by the Kazan Federal University Strategic Academic Leadership Program(PRIORITY-2030).
文摘Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.
文摘Objective:To analyze the efficacy of allergen subcutaneous injection immunotherapy in patients with allergic rhinitis.Methods:Fifty patients with allergic rhinitis admitted from May 2023 to May 2025 were selected as study subjects and randomly divided into a control group and an observation group,with 25 patients in each group.The control group was treated with budesonide nasal spray,while the observation group received allergen subcutaneous injection immunotherapy in addition to the control treatment.The treatment efficacy,adverse reactions,symptom improvement time,and immune indicators were compared between the two groups.Results:The observation group showed a higher disease treatment efficacy than the control group(p<0.05);the incidence of adverse reactions in the observation group was not statistically significant compared to the control group(p>0.05);the observation group had a shorter symptom improvement time for nasal obstruction,rhinorrhea,and sneezing than the control group(p<0.05);before treatment,there was no statistical significance in immune indicators between the two groups(p>0.05);after treatment,CD3+and CD4/CD8+in the observation group were higher than those in the control group(p<0.05).Conclusion:Allergen subcutaneous injection immunotherapy in patients with allergic rhinitis can improve disease treatment efficacy,alleviate clinical symptoms,and enhance immune function.This therapy is safe and has clinical application value.
基金supported by the Non-communicable Chronic Diseases National Science and Technology Major Project(Grant No.2025ZD0544003).
文摘The landscape of breast cancer treatment has undergone a transformative shift with the integration of immunotherapy.Historically considered a“cold”tumor with limited immunogenicity,breast cancer management was dominated by surgery,chemotherapy,radiotherapy,and targeted therapies1.However,the advent of immune checkpoint inhibitors(ICIs)has challenged this paradigm,opening a new frontier.The initial breakthrough in triple-negative breast cancer(TNBC)demonstrated that a subset of patients could derive profound and durable clinical benefit from pembrolizumab and atezolizumab2,3.Today,precision immunotherapy aims to identify the patients most likely to respond,to convert immunologically silent tumors into responsive tumors,and to strategically combine immunotherapies with other modalities to overcome resistance.This evolution from empirical application to biomarker-driven strategies marks the critical juncture at which we stand,transitioning promising clinical trial data into refined,effective,and accessible clinical practice4.Recent key clinical studies on breast cancer immunotherapy are summarized in Table 1.
基金supported by the National Natural Science Foundation of China(82441036)Ganzhou Municipal Science and Technology Project(2022-RC1342)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515130004)Key-Area Research and Development Program of Guangdong Province(2019B020234003)Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)Open Project Fund Project of Guangdong Academy of Medical Sciences(YKY-KF202210).
文摘Background:Thimerosal is a mercury-containing preservative widely used in vaccines.This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies,particularly colorectal cancer(CRC)and melanoma.Methods:A combination of in vitro and in vivo approaches was employed.Cell proliferation,apoptosis,migration,and invasion were assessed using Cell Counting Kit-8(CCK-8),colony formation,ATP viability,Western blotting,flow cytometry,wound-healing and Transwell assays.Subcutaneous,lung metastases,and Azoxymethane/Dextran Sulfate Sodium Salt(AOM/DSS)-induced colitis-associated CRC models were established to examine antitumor efficacy and safety.The functional role of mercury ions was validated using structural analogues.Mechanistic studies included RNA sequencing,Western blot,and immunohistochemical analysis of CD8^(+)T cell infiltration.The synergistic effect with programmed cell death protein 1(PD-1)antibody therapy was also evaluated.Results:Thimerosal potently inhibited tumor growth(with IC_(50) values ranging from 0.1 to 1μM in vitro)and significantly prolonged survival without overt toxicity in vivo.Mechanistically,mercury ions were identified as critical functional sites mediating Thimerosal’s antitumor effects.Specifically,Thimerosal inhibited the phosphorylation of Janus kinase 1(JAK1)and signal transducer and activator of transcription 3(STAT3).Furthermore,it enhanced the infiltration of CD8^(+)T cells into the tumor microenvironment and synergistically augmented the efficacy of anti-PD-1 therapy.Conclusion:Thimerosal exerts dual antitumor roles by direct JAK1/STAT3 inhibition and immune modulation via CD8^(+)T cell recruitment.It represents a promising repurposed drug and immunotherapeutic adjuvant for CRC and melanoma.
文摘Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.
基金supported by the Natural Scientific Foundation of Zhejiang Province,China(Grant No.LTGY23H160007).
文摘Objective:Immune checkpoint inhibitors(ICIs)have demonstrated substantial efficacy in patients with advanced non-small cell lung cancer(NSCLC).However,the optimal duration of ICI therapy remains unclear,and limited real-world data are available.The aim of this study was to evaluate the relationship between ICI therapy duration and overall survival(OS)in patients who achieved varying best overall response(BOR)during ICI treatment,and to compare patients treated for 6 to 18 months vs.at least 18 months.Methods:This retrospective cohort study included adult patients diagnosed with advanced NSCLC who received ICI therapy at the Zhejiang Cancer Hospital between 2017 and 2022.Data collection ended on May 1,2024,and statistical analysis was performed between May and June 2024.Results:Using strict entry criteria,we screened 487 patients with advanced NSCLC and identified 134 eligible patients.Among these patients,the median durations of immunotherapy and follow-up were 24.57 months and 43.60 months,respectively.The objective response rate(ORR)was 58.2%,and the median progression-free survival(PFS)was 10.6 months.Median OS was not reached.At the last follow-up,54 patients had no disease progression,and 118 patients remained alive.Patients treated with ICI therapy for≥18 months had superior survival to those treated for 6 to 18 months(P=0.039).Further analysis revealed that the survival benefit was associated with BOR during ICI therapy.Specifically,patients achieving complete response/partial response(CR/PR)who received≥18 months of ICI therapy had a trend toward longer median OS than those treated for 6 to 18 months,but the difference did not reach statistical significance(P=0.177).Patients with stable disease(SD)who received≥18 months of ICI therapy had a statistically longer median OS than those treated for 6 to 18 months(P=0.019).Among patients treated with ICIs for≥18 months,24 continued with ICI-based therapy and achieved a median PFS2 of 6.67 months,an ORR of 33.3%,and a disease control rate(DCR)of 83.3%.Conclusions:This study provides real-world evidence and novel insights into the need for continuing ICI therapy beyond 18 months in patients with advanced NSCLC who do not exhibit progressive disease.For patients achieving SD during ICI therapy,a treatment duration of at least 18 months appears appropriate.For patients achieving CR/PR,treatment decisions should be individualized according to patient-specific circumstances.However,owing to the retrospective study design,potential selection bias and confounding factors might have influenced the results.Therefore,our findings require further validation in prospective clinical studies.
文摘Primary liver cancer(PLC)is a prevalent malignancy with high incidence and mortality rates globally.Hepatocellular carcinoma(HCC),primarily resulting from hepatitis B virus infections in Asia,constitutes most PLC cases.Despite advancements in targeted therapies and localized treatments,the 5-year survival rate remains low,indicating limited efficacy of current approaches.The advent of immunotherapy,particularly immune checkpoint inhibitors(ICIs),has brought new hope for patients with PLC.However,the liver's unique immune microenvironment presents significant challenges to the effectiveness of immunotherapy in HCC.This article reviews recent research developments in liver cancer immunotherapy,focusing on ICIs,combination therapies,emerging treatments,and prospective future directions.
基金supported by the National Science Foundation of China(No.82172726)the Youth Project of Science and Technology Department of Shanxi Province(No.202203021212105)the Research Project Supported by the Shanxi Scholarship Council of China(2021-156).
文摘Conventional therapies are primary cancer treatments that directly eliminate or inhibit the growth of tumor cells,reducing the overall tumor burden.Increasing evidence suggests that conventional therapies possess significant immunomodulatory properties in addition to their established direct tumoricidal effects.Emerging immunotherapies have revolutionized the clinical management of various cancer types.Conventional therapy and immunotherapy have demonstrated remarkable clinical efficacy,leading to numerous ongoing clinical investiga-tions exploring their potential synergistic effects.However,trials investigating the combination of conventional therapy and immunotherapy have shown limited synergistic therapeutic efficacy.This unsatisfactory clinical outcome may be attributed to the suboptimal design of the combination approach and the inadequate understanding of the mechanisms and impacts of radiotherapy,chemotherapy,targeted ther-apy regimens(including dosing,timing,and administration route),and surgery on both cancer cells and the host immune system.Here,we comprehensively review preclinical and clinical investigations exploring the therapeutic effects and mechanisms of conventional therapy alone or in combination with immunotherapy.We proposed that optimizing the dosing,timing,and route of administration of conventional therapies can enhance the synergistic efficacy of combination therapies,thus offering significant clinical advantages.
文摘Allergen specific immunotherapy(AIT)has a history spanning over 110 years and represents the only diseasemodifying treatment for allergic diseases,with potential preventive effects.Nevertheless,the broader application of AIT is limited by the inherent drawbacks of natural allergen extracts,such as variability in composition,risk of side effects,and complex,lengthy treatment regimens.Advances in molecular allergology have enabled the development of novel vaccine strategies-including recombinant allergens,hypoallergenic derivatives,allergen-derived peptides,and nucleic acid-based vaccines-that aim to improve safety,efficacy,and precision.However,no molecule-based AIT product has yet achieved regulatory approval,largely due to technical and clinical trial challenges.In parallel,immunomodulatory adjuvants such as monophosphoryl lipid A,CpG oligodeoxynucleotides,flagellin and mannan have demonstrated promising properties.These innovations have the potential to enhance AIT outcomes by promoting immune tolerance,reducing IgE responses,and improving patient compliance.This review summarizes the current landscape of allergen vaccines and adjuvant technologies under investigation for AIT,highlighting key advances,clinical data,and future directions aimed at overcoming existing limitations and optimizing treatment strategies for allergic diseases.
文摘Cancer is a major global concern due to its high mortality rate.Tumor immunotherapy has revolutionized cancer treatment.However,low response rates and immune-related complications remain challenges.Extracellular vesicles(EVs),including exosomes,have emerged as promising therapeutic tools for various pathological conditions,especially cancer.Evidence indicates that changes in the quantity and composition of EVs can influence the immunosuppressive tumor microenvironment,potentially affecting the effectiveness of immunotherapy.Exploiting EVs for immune sensitization has generated significant clinical interest.This review provides an in-depth understanding of the origin of EVs,their therapeutic applications(such as drug delivery nanoplatforms and cancer immunotherapies,including vaccines),diagnostic potential as tumor biomarkers,ongoing EV-based clinical trials,and the challenges encountered in EV-based cancer immunotherapy.
基金National Natural Science Foundation of China,No.82073192 and No.82273231Beijing Science and Technology Program,No.Z221100007422125The Chinese People's Liberation Army General Hospital Medical Engineering Laboratory Project,No.2022SYSZZKY16.
文摘BACKGROUND Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer(GC).A comprehensive review of advancements,current status,and research trends in GC immunotherapy is essential to inform future investigative efforts.AIM To delineate the trends,advancements,and focal points in immunotherapy for GC.METHODS We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20,2023,indexed in the Web of Science Core Collection.Data analysis and visualization were facilitated by CiteSpace(6.1.6R),VOSviewer v.1.6.17,and GraphPad Prism v8.0.2.RESULTS There has been an increase in the annual publication rate of GC immunotherapy research.China leads in publication volume,while the United States demonstrates the highest citation impact.Fudan University is notable for its citation frequency and publication output.Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis,the tumor microenvironment(TME),and integrative immunotherapy with targeted therapy.Emerging research areas include gastroesophageal junction cancer,adoptive immunotherapy,and the role of Treg cell in immunotherapy.CONCLUSION GC immunotherapy research is an expanding field attracting considerable scientific interest.With the clinical adoption of immunotherapy in GC,the primary goals are to enhance treatment efficacy and patient outcomes.Unlike hematological malignancies,GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells.For instance,although CAR-T therapy is effective in hematological malignancies,it has underperformed in GC settings.Current research is centered on overcoming immunosuppression within the TME,with a focus on combinations of targeted therapy,adoptive immunotherapy,Treg cell dynamics,and precise prognosis prediction in immunotherapy.Additionally,immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.
