Hepatitis B virus （HBV） infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of...Hepatitis B virus （HBV） infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection： （1） These influence acquisition of chronic HBV carrier state, （2） They are important in the context of liver damages, （3） Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach （vaccine therapy）. The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV- specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.展开更多
Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination ...Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A （CsA） on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada＇s technique. Recipients were divided into group A （control group）： SD→SD; group B （group of rejection）： SD→Wistar without any treatment; group C： SD→Wistar with CsA monotherapy from day 1 to day 5; and group D： SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A （〉60 days） and D （〉60 days） was significantly longer than that in group B （13.8±2.4 days）. The serum levels of interleukin 2 （IL-2） and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor a was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B （P〈0.05）.Conclusions Combined immune therapy can prolong the survival of al log rafts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.展开更多
Adoptive immunotherapy involving the transfer of autologous tumor or virus-reactive T lymphocytes has been demonstrated to be effective in the eradication of cancer and virally infected cells. Identification of MHC-re...Adoptive immunotherapy involving the transfer of autologous tumor or virus-reactive T lymphocytes has been demonstrated to be effective in the eradication of cancer and virally infected cells. Identification of MHC-restricted antigens and progress in generation of adaptive immune responses have provided new direction for such treatment for severe pathologies such as cancer and autoimmune diseases. Here we review the latest development about the molecular basis of MHC-I/TCR interaction, and it＇s manipulation including enhanced MHC-I expression, modification of peptide and engineered TCR for clinical applications such as vaccine design, tumor therapy and autoimmune diseases.展开更多
Objective:Well-defined germ-line mutations in thePTCH1 gene are associated with syndromic multiple basal cell carcinomas(BCCs).Here,we used whole exome sequencing(WES)to identify the role of patched-1 in patients with...Objective:Well-defined germ-line mutations in thePTCH1 gene are associated with syndromic multiple basal cell carcinomas(BCCs).Here,we used whole exome sequencing(WES)to identify the role of patched-1 in patients with multiple,unusually large BCCs.Methods:A 72-year old patient presenting with numerous BCCs progressing to large ulcerating lesions was enrolled.WES was used to identify the pathogenic gene locus.Results:Genetic work-up by WES identified a homozygousPTCH1 nonsense mutation in the tumor tissue but not present in her blood cells or in non-lesional skin.In addition,heterozygous missense mutations were identified in three cancer-associated genes(EPHB2,RET,andGALNT12)in blood cells as well as in lesional and non-lesional skin.We also tested systemic immune therapy as a potentially beneficial approach to treat patients with numerous large BCCs on scatted areas of involvement.A rapid and sustained response to nivolumab was noted,suggesting that it is an efficacious drug for long-term therapeutic outcome.Conclusion:PTCH1,EPHB2,RET,andGALNT12 may potentially contribute to the synergistic oncogene driven malignant transformation manifesting as multiple,unusually large BCCs.展开更多
Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment(TME).Some bacteria exhibit spontaneous chemotaxis to-ward the anaerobic and immune-...Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment(TME).Some bacteria exhibit spontaneous chemotaxis to-ward the anaerobic and immune-suppressive TME,which makes them ideal natural vehicles for cancer gene therapy.Here,we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2(Il2)expression plasmid onto the surface of VNP20009,an attenuated Salmonella typhimur-ium strain with well-documented anti-cancer activity,and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella.Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Sal-monella maintained the tumor-targeting feature of bacteria,and could be effectively phagocytosed by in-tratumoral macrophages,thus leading to the expression and secretion of IL2 in TME.The detailed analysis of tumor immune microenvironment(TIME)showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME,marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME,thus leading to significant anti-tumor effects in melanoma,orthotopic hepatocellular carcinoma,and pulmonary metastasis models.More importantly,Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems.Taken together,we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effec-tive TME-targeted delivery of therapeutic gene,as well as synergistic re-activation of TIME.展开更多
Chimeric antigen receptor T(CAR-T)cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies.There are several key components c...Chimeric antigen receptor T(CAR-T)cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies.There are several key components critical for development and application of CAR-T therapy.First,the design of CAR vectors can considerably affect several aspects of the physiological functions of these T cells.Moreover,despite the wide use of g-retrovirus and lentivirus in mediating gene transfer into T cells,optimal CAR delivery systems are also being developed and evaluated.In addition,several classes of mouse models have been used to evaluate the efficacies of CART cells;however,each model has its own limitations.Clinically,although surprising complete remission(CR)rates were observed in acute lymphoblastic leukemia(ALL),lymphoma,and multiple myeloma(MM),there is still a lack of specific targets for acute myeloid leukemia(AML).Leukemia relapse remains a major challenge,and its mechanism is presently under investigation.Cytokine release syndrome(CRS)and neurotoxicity are life-threatening adverse effects that need to be carefully treated.Several factors that compromise the activities of anti-solid cancer CAR-T cells have been recognized,and further improvements targeting these factors are the focus of the development of novel CAR-T cells.Overcoming the current hurdles will lead to optimal responses of CAR-T cells,thus paving the way for their wide clinical application.展开更多
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatoc...Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.展开更多
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HB...Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin BI) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement or in part replace the existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduced HCC incidence and an improved clinical outcome for patients with HCC, one of the most devastating malignancies worldwide.展开更多
As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malig...As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.展开更多
Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-...Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.展开更多
The difficulty of early diagnosis,high tumor heterogeneity,and high recurrence and metastasis rates lead to an unsatisfactory treatment status for hepatocellular carcinoma(HCC).HCC is a typical inflammation-driven tum...The difficulty of early diagnosis,high tumor heterogeneity,and high recurrence and metastasis rates lead to an unsatisfactory treatment status for hepatocellular carcinoma(HCC).HCC is a typical inflammation-driven tumor.Chronic inflammation allows nascent tumors to escape immunosurveillance.Chemokines are small,soluble,secreted proteins that can regulate the activation and trafficking of immune cells during inflammation.Several studies have shown that various chemokines with overarching functions disrupt the immune microenvironment during the initiation and progression of HCC.The dysregulated chemokine network in HCC contributes to multiple malignant processes,including angiogenesis,tumor proliferation,migration,invasion,tumor low response,and resistance to immune therapy.Here,we summarize the current studies focusing on the role of chemokines and their receptors in the HCC immune microenvironment,highlighting potential translational therapeutic uses for modulating the chemokine system in HCC.展开更多
Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis a...Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.展开更多
Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated ...Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated to this exciting field, and focused on new progress in personalized drug development and antibody drug against checkpoint pathway. Tais meeting report summarizes the key developments presented and discussed at the meeting, with a focus on immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal antibody drugs intervening these checkpoint pathways have the potential to play a larger role in personalize medicine within the near future. Here we intended to provide a comprehensive summary about ongoing trends and future perspectives on personalized medicine in cancer therapy.展开更多
Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increa...Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.展开更多
Regulatory T(Treg)cells,a subtype of immunosuppressive CD4^+T cells,are vital for maintaining immune homeostasis in healthy people.Forkhead box protein P3(FOXP3),a member of the forkhead-wingedhelix family,is the pivo...Regulatory T(Treg)cells,a subtype of immunosuppressive CD4^+T cells,are vital for maintaining immune homeostasis in healthy people.Forkhead box protein P3(FOXP3),a member of the forkhead-wingedhelix family,is the pivotal transcriptional factor of Treg cells.The expression,post-translational modifications,and protein complex of FOXP3 present a great impact on the functional stability and immune plasticity of Treg cells in vivo.In particular,the mutation of FOXP3 can result in immune dysregulation,polyendocrinopathy,enteropathy,X-linked(IPEX)syndrome,which is a rare genetic disease mostly diagnosed in early childhood and can soon be fatal.IPEX syndrome is related to several manifestations,including dermatitis,enteropathy,type 1 diabetes,thyroiditis,and so on.Here,we summarize some recent findings on FOXP3 regulation and Treg cell function.We also review the current knowledge about the underlying mechanism of FOXP3 mutant-induced IPEX syndrome and some latest clinical prospects.At last,this review offers a novel insight into the role played by the FOXP3 complex in potential therapeutic applications in IPEX syndrome.展开更多
Human colorectal cancer(CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves surv...Human colorectal cancer(CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy.展开更多
Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multip...Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.展开更多
BACKGROUND Gut microbiome(GM)composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy(ICB)and of ICBrelated colitis.AIM To conduct a systematic review on th...BACKGROUND Gut microbiome(GM)composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy(ICB)and of ICBrelated colitis.AIM To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB.METHODS The review protocol was registered in PROSPERO:CRD42021228018.From a total of 300 studies,nine studies met inclusion criteria.Two studies were phase I clinical trials,while the remainder were prospective observational studies.All but one study has moderate risk of bias.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS Fecal samples enriched in Firmicutes phylum were associated with good response to ICB,whereas the Bacteroidales family was associated with poor response to ICB.Samples with greater GM diversity were associated with more favorable response to ICB[hazard ratio(HR)=3.57,95%confidence interval=1.02-12.52,P<0.05].Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis(P<0.01)whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis(P<0.05).Overall,there was limited concordance in the organisms in the GM identified to be associated with response to ICB,and studies evaluating GM diversity showed conflicting results.CONCLUSION This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.展开更多
Gallbladder cancer(GBC)is a rare but aggressive cancer that often presents subtle early symptoms,leading to late-stage diagnosis.In recent years,significant advan-cements have been made in early detection and treatmen...Gallbladder cancer(GBC)is a rare but aggressive cancer that often presents subtle early symptoms,leading to late-stage diagnosis.In recent years,significant advan-cements have been made in early detection and treatment of GBC.These improvements are driven by a better understanding of the risk factors for this malignancy and the use of new diagnostic technologies.This review systemat-ically examines the risk factors associated with GBC,and advancements in diagnostic techniques and treatment strategies,with an aim to enhance the early diagnosis and effective management of GBC to provide a valuable reference for clinical practice.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
基金Supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan to Sk. Md. Fazle Akbar, No. C17590651 and Morikazu Onji, No. C17590652
文摘Hepatitis B virus （HBV） infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection： （1） These influence acquisition of chronic HBV carrier state, （2） They are important in the context of liver damages, （3） Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach （vaccine therapy）. The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV- specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.
文摘Background The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A （CsA） on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.Methods The model of rat orthotopic liver transplantation was established by modified Kamada＇s technique. Recipients were divided into group A （control group）： SD→SD; group B （group of rejection）： SD→Wistar without any treatment; group C： SD→Wistar with CsA monotherapy from day 1 to day 5; and group D： SD→Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.Results The survival period of recipients in groups A （〉60 days） and D （〉60 days） was significantly longer than that in group B （13.8±2.4 days）. The serum levels of interleukin 2 （IL-2） and interferon y in group B were significantly higher than those in other groups; the level of tumor necrosis factor a was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B （P〈0.05）.Conclusions Combined immune therapy can prolong the survival of al log rafts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.
文摘Adoptive immunotherapy involving the transfer of autologous tumor or virus-reactive T lymphocytes has been demonstrated to be effective in the eradication of cancer and virally infected cells. Identification of MHC-restricted antigens and progress in generation of adaptive immune responses have provided new direction for such treatment for severe pathologies such as cancer and autoimmune diseases. Here we review the latest development about the molecular basis of MHC-I/TCR interaction, and it＇s manipulation including enhanced MHC-I expression, modification of peptide and engineered TCR for clinical applications such as vaccine design, tumor therapy and autoimmune diseases.
基金The study was supported by NIH R01 IA143810the Department of Dermatology and Cutaneous Biology,Thomas Jefferson University Institutional funds.
文摘Objective:Well-defined germ-line mutations in thePTCH1 gene are associated with syndromic multiple basal cell carcinomas(BCCs).Here,we used whole exome sequencing(WES)to identify the role of patched-1 in patients with multiple,unusually large BCCs.Methods:A 72-year old patient presenting with numerous BCCs progressing to large ulcerating lesions was enrolled.WES was used to identify the pathogenic gene locus.Results:Genetic work-up by WES identified a homozygousPTCH1 nonsense mutation in the tumor tissue but not present in her blood cells or in non-lesional skin.In addition,heterozygous missense mutations were identified in three cancer-associated genes(EPHB2,RET,andGALNT12)in blood cells as well as in lesional and non-lesional skin.We also tested systemic immune therapy as a potentially beneficial approach to treat patients with numerous large BCCs on scatted areas of involvement.A rapid and sustained response to nivolumab was noted,suggesting that it is an efficacious drug for long-term therapeutic outcome.Conclusion:PTCH1,EPHB2,RET,andGALNT12 may potentially contribute to the synergistic oncogene driven malignant transformation manifesting as multiple,unusually large BCCs.
基金supported by“Pioneer”and“Leading Goose”R&D Program of Zhejiang Province(2022C03004 to Jianxiang Chen,China),Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022029C to Yiting Qiao,China),National Natural Science Foundation of China(82373888 to Yiting Qiao,82072646,82372664 to Jianxiang Chen),Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT320-02 to Yiting Qiao,China)The joint foundation of National Administration of Traditional Chinese Medicine&Zhejiang Province-major project(GZY-ZJ-KJ-24045 to Jianxiang Chen,China)+1 种基金Research Unit Project of Chinese Academy of Medical Sciences(2019‒I2M‒5‒030 to Shusen Zheng,China)Postgraduate research innovation project of Hangzhou Normal University(2022HSDYJ SKY244 to Yunxin Pei,2022HSDYJ SKY015 to Menglan Wang,China).
文摘Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment(TME).Some bacteria exhibit spontaneous chemotaxis to-ward the anaerobic and immune-suppressive TME,which makes them ideal natural vehicles for cancer gene therapy.Here,we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2(Il2)expression plasmid onto the surface of VNP20009,an attenuated Salmonella typhimur-ium strain with well-documented anti-cancer activity,and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella.Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Sal-monella maintained the tumor-targeting feature of bacteria,and could be effectively phagocytosed by in-tratumoral macrophages,thus leading to the expression and secretion of IL2 in TME.The detailed analysis of tumor immune microenvironment(TIME)showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME,marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME,thus leading to significant anti-tumor effects in melanoma,orthotopic hepatocellular carcinoma,and pulmonary metastasis models.More importantly,Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems.Taken together,we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effec-tive TME-targeted delivery of therapeutic gene,as well as synergistic re-activation of TIME.
基金The National Major Scientific and Technological Special Project for“Significant New Drugs Development,”No.SQ2018ZX090201The Strategic Priority Research Program of the Chinese Academy of Sciences,Grant No.XDB19030205,No.XDA12050305+10 种基金Guangdong Provincial Applied Science and Technology Research&Development Program,No.2016B020237006Guangdong Special Support Program,NO.2017TX04R102Frontier and key technology innovation special grant from the Department of Science and Technology of Guangdong province,No.2015B020227003Natural Science Fund of Guangdong Province:Distinguished Young Scholars(Grant No.:2014A030306028)Doctoral Foundation,No.:2017A030310381National Natural Science Foundation of China(NSFC),No.81773301,81700156,81870121,81873847Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory,No.2018GZR110105003Science and Technology Planning Project of Guangdong Province,China(2017B030314056)Guangzhou Medical University High-level University Construction Research Startup Fund,NO.B195002004013Research Program of Hefei Institute of Stem Cell and Regenerative Medicine,No.2019YF001Guangzhou science and technology plan project,NO.201907010042,201904010473.
文摘Chimeric antigen receptor T(CAR-T)cells have emerged as novel and promising immune therapies for the treatment of multiple types of cancer in patients with hematological malignancies.There are several key components critical for development and application of CAR-T therapy.First,the design of CAR vectors can considerably affect several aspects of the physiological functions of these T cells.Moreover,despite the wide use of g-retrovirus and lentivirus in mediating gene transfer into T cells,optimal CAR delivery systems are also being developed and evaluated.In addition,several classes of mouse models have been used to evaluate the efficacies of CART cells;however,each model has its own limitations.Clinically,although surprising complete remission(CR)rates were observed in acute lymphoblastic leukemia(ALL),lymphoma,and multiple myeloma(MM),there is still a lack of specific targets for acute myeloid leukemia(AML).Leukemia relapse remains a major challenge,and its mechanism is presently under investigation.Cytokine release syndrome(CRS)and neurotoxicity are life-threatening adverse effects that need to be carefully treated.Several factors that compromise the activities of anti-solid cancer CAR-T cells have been recognized,and further improvements targeting these factors are the focus of the development of novel CAR-T cells.Overcoming the current hurdles will lead to optimal responses of CAR-T cells,thus paving the way for their wide clinical application.
文摘Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.
文摘Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin BI) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement or in part replace the existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduced HCC incidence and an improved clinical outcome for patients with HCC, one of the most devastating malignancies worldwide.
基金the Key Program of the National Natural Science Foundation(NNSF)of China(No.81230052 and No.81630006).
文摘As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.
文摘Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.
基金Supported by grants from the National Natural Science Foundation of China(No.81871911[W.H.],No.81772623[L.X.],and No.81972237[L.X.])the National Key Research and Development Program of China(No.2018YFC1312103[L.X.]).
文摘The difficulty of early diagnosis,high tumor heterogeneity,and high recurrence and metastasis rates lead to an unsatisfactory treatment status for hepatocellular carcinoma(HCC).HCC is a typical inflammation-driven tumor.Chronic inflammation allows nascent tumors to escape immunosurveillance.Chemokines are small,soluble,secreted proteins that can regulate the activation and trafficking of immune cells during inflammation.Several studies have shown that various chemokines with overarching functions disrupt the immune microenvironment during the initiation and progression of HCC.The dysregulated chemokine network in HCC contributes to multiple malignant processes,including angiogenesis,tumor proliferation,migration,invasion,tumor low response,and resistance to immune therapy.Here,we summarize the current studies focusing on the role of chemokines and their receptors in the HCC immune microenvironment,highlighting potential translational therapeutic uses for modulating the chemokine system in HCC.
文摘Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.
文摘Personalized cancer medicine has seen significant improvements over the past decade. Recent Elsevier conference： Miami winter symposium 2015 （MWS2015） ＂Towards Personalized Cancer Medicine＂ meeting was dedicated to this exciting field, and focused on new progress in personalized drug development and antibody drug against checkpoint pathway. Tais meeting report summarizes the key developments presented and discussed at the meeting, with a focus on immunotherapy, especially on the CTLA-4 and PD-1/PD-L1 pathways. The monoclonal antibody drugs intervening these checkpoint pathways have the potential to play a larger role in personalize medicine within the near future. Here we intended to provide a comprehensive summary about ongoing trends and future perspectives on personalized medicine in cancer therapy.
文摘Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.
基金supported by National Natural Science Foundation of China(grants:81830051,31525008,31670911 and 31961133011)Shanghai Academic Research Leader 16XD1403800+1 种基金Shanghai Jiao Tong University(SJTU)-The Chinese University of Hong Kong(CUHK)Joint Research Collaboration Fundthe Fundamental Research Funds for Central Universities.
文摘Regulatory T(Treg)cells,a subtype of immunosuppressive CD4^+T cells,are vital for maintaining immune homeostasis in healthy people.Forkhead box protein P3(FOXP3),a member of the forkhead-wingedhelix family,is the pivotal transcriptional factor of Treg cells.The expression,post-translational modifications,and protein complex of FOXP3 present a great impact on the functional stability and immune plasticity of Treg cells in vivo.In particular,the mutation of FOXP3 can result in immune dysregulation,polyendocrinopathy,enteropathy,X-linked(IPEX)syndrome,which is a rare genetic disease mostly diagnosed in early childhood and can soon be fatal.IPEX syndrome is related to several manifestations,including dermatitis,enteropathy,type 1 diabetes,thyroiditis,and so on.Here,we summarize some recent findings on FOXP3 regulation and Treg cell function.We also review the current knowledge about the underlying mechanism of FOXP3 mutant-induced IPEX syndrome and some latest clinical prospects.At last,this review offers a novel insight into the role played by the FOXP3 complex in potential therapeutic applications in IPEX syndrome.
文摘Human colorectal cancer(CRC) is the third most commonly diagnosed malignancies and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although new chemotherapeutic regimen improves survival rates, therapy with better efficacy and less adverse effects is drastically needed. Immunotherapy has been investigated in human CRC for decades with limited success. However, recent developments of immunotherapy, particularly immune checkpoint inhibitor therapy, have achieved promising clinical benefits in many types of cancer and revived the hope for utilizing such therapy in human CRC. In this review, we will discuss important immunological landscape within the CRC microenvironment and introduce immunoscore system to better describe immunophenotyping in CRC. We will also discuss different immunotherapeutic approaches currently utilized in different phases of clinical trials. Some of those completed or ongoing trials are summarized. Finally, we provide a brief prospective on the future human CRC immunotherapy.
基金This work was supported by the National Key R&D Program of China(Grant No.2018YFC1313300)the National Natural Science Foundation of China(Grant No.81572331).
文摘Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.
文摘BACKGROUND Gut microbiome(GM)composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy(ICB)and of ICBrelated colitis.AIM To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB.METHODS The review protocol was registered in PROSPERO:CRD42021228018.From a total of 300 studies,nine studies met inclusion criteria.Two studies were phase I clinical trials,while the remainder were prospective observational studies.All but one study has moderate risk of bias.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).RESULTS Fecal samples enriched in Firmicutes phylum were associated with good response to ICB,whereas the Bacteroidales family was associated with poor response to ICB.Samples with greater GM diversity were associated with more favorable response to ICB[hazard ratio(HR)=3.57,95%confidence interval=1.02-12.52,P<0.05].Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis(P<0.01)whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis(P<0.05).Overall,there was limited concordance in the organisms in the GM identified to be associated with response to ICB,and studies evaluating GM diversity showed conflicting results.CONCLUSION This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.
基金Supported by the Program for Young Backbone Teachers in the Universities of Anhui Province,No.JNFX2023031.
文摘Gallbladder cancer(GBC)is a rare but aggressive cancer that often presents subtle early symptoms,leading to late-stage diagnosis.In recent years,significant advan-cements have been made in early detection and treatment of GBC.These improvements are driven by a better understanding of the risk factors for this malignancy and the use of new diagnostic technologies.This review systemat-ically examines the risk factors associated with GBC,and advancements in diagnostic techniques and treatment strategies,with an aim to enhance the early diagnosis and effective management of GBC to provide a valuable reference for clinical practice.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
