Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id...Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.展开更多
Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to lo...Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.展开更多
Background A hepatic adverse event(HAE)is defined as a liver injury that occurs following immune checkpoint inhibitor(ICI)administration in oncology Patients.Immune-mediated hepatotoxicity(IMH)is a type of HAE directl...Background A hepatic adverse event(HAE)is defined as a liver injury that occurs following immune checkpoint inhibitor(ICI)administration in oncology Patients.Immune-mediated hepatotoxicity(IMH)is a type of HAE directly caused by ICI and is associated with immune system hyperactivation.HAE incidence varies across different clinical studies.This study aimed to explore the risk factors of HAE and establish a personalized IMH treatment strategy.Methods Randomized controlled trials(RCTs)on ICIs and case reports related to IMH were collected and summarized separately.Meta-analysis was performed using Review Manager(version 5.0),whereas correlation analysis and linear regression were performed using SPSS(version 24.0)to evaluate any correlations between the two variables.Results Overall,36 RCTs containing 18,515 patients and 39 case reports met our inclusion criteria.The ICI administration increased the HAE risk(risk ratio[RR]=1.40)as well as severe HAE(RR=2.55).The overall HAE incidence and severe incidence were about 15.3%and 4.3%,respectively.Cytotoxic T-lymphocyte-associated protein 4(CTLA-4)inhibitors have a higher incidence of HAE than programmed cell death protein 1(PD-1)and programmed death-ligand 1(PD-L1)inhibitors.Finally,we found a positive correlation between the onset time of IMH and the recovery time of liver injury.Conclusions ICI administration increased the incidence risk of HAE,especially in patients treated with CTLA-4 inhibitors.Regarding IMH treatment,the glucocorticoid dosage must be individually reduced according to the severity and onset time of HAE.展开更多
After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking ...After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new "immunotherapy era" with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade.展开更多
The advent of immunotherapy and the development of immune checkpoint inhibitors(ICIs)are changing the way we think about cancer treatment.ICIs have shown clinical benefits in a variety of tumor types,and ICI-based imm...The advent of immunotherapy and the development of immune checkpoint inhibitors(ICIs)are changing the way we think about cancer treatment.ICIs have shown clinical benefits in a variety of tumor types,and ICI-based immunotherapy has shown effective clinical outcomes in immunologically“hot”tumors.However,for immunologically“cold”tumors such as colorectal cancer(CRC),only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates.In this review,we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC,and summarize the treatment strategies and challenges of immunotherapy for cold CRC.We also explain the mechanism,biology,and role of immunotherapy for cold CRC,which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.展开更多
One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectom...One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.展开更多
Introduction
Cancer cells can avoid being recognized and destroyed by the immune system by activating im-mune checkpoints, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and the programmed death-1 (PD-1)...Introduction
Cancer cells can avoid being recognized and destroyed by the immune system by activating im-mune checkpoints, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and the programmed death-1 (PD-1) receptor and its ligand PD-L1.展开更多
基金the Huzhou Science and Technology Bureau,Zhejiang Province,China(2020GZ41).
文摘Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
基金Supported by The National Key Research and Development Program,No.2022YFC2603500 and No.2022YFC2603505Beijing Municipal Health Commission High-Level Public Health Technical Personnel Construction Project,No.Discipline leader-03-26+2 种基金The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority,No.XXZ0302The Capital Health Research and Development of Special Public Health Project,No.2022-1-2172and Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.XMLX 202127.
文摘Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.
文摘Background A hepatic adverse event(HAE)is defined as a liver injury that occurs following immune checkpoint inhibitor(ICI)administration in oncology Patients.Immune-mediated hepatotoxicity(IMH)is a type of HAE directly caused by ICI and is associated with immune system hyperactivation.HAE incidence varies across different clinical studies.This study aimed to explore the risk factors of HAE and establish a personalized IMH treatment strategy.Methods Randomized controlled trials(RCTs)on ICIs and case reports related to IMH were collected and summarized separately.Meta-analysis was performed using Review Manager(version 5.0),whereas correlation analysis and linear regression were performed using SPSS(version 24.0)to evaluate any correlations between the two variables.Results Overall,36 RCTs containing 18,515 patients and 39 case reports met our inclusion criteria.The ICI administration increased the HAE risk(risk ratio[RR]=1.40)as well as severe HAE(RR=2.55).The overall HAE incidence and severe incidence were about 15.3%and 4.3%,respectively.Cytotoxic T-lymphocyte-associated protein 4(CTLA-4)inhibitors have a higher incidence of HAE than programmed cell death protein 1(PD-1)and programmed death-ligand 1(PD-L1)inhibitors.Finally,we found a positive correlation between the onset time of IMH and the recovery time of liver injury.Conclusions ICI administration increased the incidence risk of HAE,especially in patients treated with CTLA-4 inhibitors.Regarding IMH treatment,the glucocorticoid dosage must be individually reduced according to the severity and onset time of HAE.
文摘After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new "immunotherapy era" with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade.
文摘The advent of immunotherapy and the development of immune checkpoint inhibitors(ICIs)are changing the way we think about cancer treatment.ICIs have shown clinical benefits in a variety of tumor types,and ICI-based immunotherapy has shown effective clinical outcomes in immunologically“hot”tumors.However,for immunologically“cold”tumors such as colorectal cancer(CRC),only a limited number of patients are currently benefiting from ICIs due to limitations such as individual differences and low response rates.In this review,we discuss the classification and differences between hot and cold CRC and the current status of research on cold CRC,and summarize the treatment strategies and challenges of immunotherapy for cold CRC.We also explain the mechanism,biology,and role of immunotherapy for cold CRC,which will help clarify the future development of immunotherapy for cold CRC and discovery of more emerging strategies for the treatment of cold CRC.
文摘One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.
文摘Introduction
Cancer cells can avoid being recognized and destroyed by the immune system by activating im-mune checkpoints, such as cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and the programmed death-1 (PD-1) receptor and its ligand PD-L1.
