A checkpointing scheme for relevant distributed real-time tasks which can be scheduled as a DAG is proposed. A typical algorithm, OSA, is selected for DAG scheduling. A new methods based a new structure, Scheduled Clu...A checkpointing scheme for relevant distributed real-time tasks which can be scheduled as a DAG is proposed. A typical algorithm, OSA, is selected for DAG scheduling. A new methods based a new structure, Scheduled Cluster Tree, is presented to calculate the slack time of each task in the task cluster. In the checkpointing scheme, the optimal checkpoint intervals which minimize the approximated failure probability are derived formally and validated experimentally. The complexity of approximated failure probability is quite small compared with that of the exact probability. Meanwhile, the consistency of the checkpointing is discussed also.展开更多
The reliability of high-performance computing(HPC)is essential for program execution stability.However,as the hardware fault rate constantly increases,fault-tolerance techniques such as Checkpoint/Restart(C/R)introduc...The reliability of high-performance computing(HPC)is essential for program execution stability.However,as the hardware fault rate constantly increases,fault-tolerance techniques such as Checkpoint/Restart(C/R)introduce significant system overhead.This paper proposes Program Error Resilience-Aware Checkpointing Mechanism(ResCheckpointer)to mitigate the overhead of the C/R mechanism.The primary motivation of ResCheckpointer is that we observe that crash proneness(i.e.,the probability of the program crashing after fault occurrence)varies significantly among inter-and intra-HPC programs,which prompts us to flexibly adjust checkpoint intervals for further C/R overhead optimization.Specifically,we first construct the graph neural network(GNN)based learning paradigms to excavate the complex error propagation and effect mechanisms hidden within the HPC program’s execution flow,and propose Crash-Predictor for efficiently predicting programs’crash proneness.Based on this,we build ResCheckpointer,which equips an intelligent checkpoint interval setting strategy for HPC programs,i.e.,denser for the crash proneness stage while sparser for the error resilience stage.Experimental results show that ResCheckpointer can achieve up to 55.37%C/R cost reduction compared with the baseline C/R mechanism.展开更多
Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollbac...Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.展开更多
A consistent checkpointing algorithm with short freezing time (SFT) is presented in this paper. It supports fault-tolerance in distributed systems. The algorithm has shorter freezing time, lower overhead, and simplici...A consistent checkpointing algorithm with short freezing time (SFT) is presented in this paper. It supports fault-tolerance in distributed systems. The algorithm has shorter freezing time, lower overhead, and simplicity of recovery. To make checkpoint time shorter, a special control message (Munblock) is used to ensure that a process can respond the checkpoint event quickly at any given time. Moreover, main memory algorithm is used to improve the concurrency of checkpointing. By using SFT, the freezing time resulted by checkpointing is less than 0.03s. Furthermore, the control message number of SFT is only O(n).展开更多
In this papert the hard problem of the thorough garbage collection in uncoordinated Checkpointing algorithms is studied. After introduction of the traditional garbage collecting scheme, with which only obsolete checkp...In this papert the hard problem of the thorough garbage collection in uncoordinated Checkpointing algorithms is studied. After introduction of the traditional garbage collecting scheme, with which only obsolete checkpoints can be discarded, it is shown that this kind of traditional method may fail to discard any checkpoint in some special cases, and it is necessary and urgent to find a thorough garbage collecting method, with which all the checkpoints useless for any future rollback-recovery including the obsolete ones can be discarded. Then, the Thorough Garbage Collection Theorem is proposed and proved, which ensures the feasibility of the thorough garbage collection, and gives the method to calculate the set of the useful checkpoints as well.展开更多
BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic f...BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
When applied to mobile computing systems,checkpoint protocols for distributed computing systems would face many new challenges, such as low wireless bandwidth, frequent disconnections, and lack of stable storage at mo...When applied to mobile computing systems,checkpoint protocols for distributed computing systems would face many new challenges, such as low wireless bandwidth, frequent disconnections, and lack of stable storage at mobile hosts. This paper proposes a novel checkpoint protocol to effectively reduce the coordinating overhead. By using a communication vector, only a few processes participate in the checkpointing event. During checkpointing, the scheme can save the time used to trace the dependency tree by sending checkpoint requests to dependent processes at once. In addition, processes are non- blocking in this scheme, since the inconsistency is resolved by the piggyback technique. Hence the unnecessary and orphan messages can be avoided. Compared with the traditional coordinated checkpoint approach, the proposed non-blocking algorithm obtains a minimal number of processes to take checkpoints. It also reduces the checkpoint latency, which brings less overhead to mobile host with limited resources.展开更多
In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptima...In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptimal clinical outcomes due to resistance.The tumor microenvironment(TME)significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells,including dendritic cells,T cells,B cells,macrophages,neutrophils,NK cells,and myeloid-derived suppressor cells(MDSCs).These non-tumor cells often exhibit two phenotypes with altered functions,and tumor cells drives their transition towards tumor promotion through tumor-education.Tumor-educated cells(TECs)are cells influenced by tumor cells,which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anticancer therapies.These cells undergo modifications in response to signals from the tumor,which can influence their roles in tumor progression.Their dynamic interactions with tumor cells contribute to the reshaping of the TME,facilitating cancer growth and immune modulation.This review summarizes research on TECs in TME,explores mechanisms related to tumor education,and discusses their role in tumor progression and immunotherapy resistance.Additionally,potential therapeutic approaches targeting these cells are also reviewed,which may complement current treatment strategies.展开更多
Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor i...Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.展开更多
Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSC...Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.展开更多
Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunoth...Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes.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
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
Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tum...Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.展开更多
Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitor...Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.展开更多
文摘A checkpointing scheme for relevant distributed real-time tasks which can be scheduled as a DAG is proposed. A typical algorithm, OSA, is selected for DAG scheduling. A new methods based a new structure, Scheduled Cluster Tree, is presented to calculate the slack time of each task in the task cluster. In the checkpointing scheme, the optimal checkpoint intervals which minimize the approximated failure probability are derived formally and validated experimentally. The complexity of approximated failure probability is quite small compared with that of the exact probability. Meanwhile, the consistency of the checkpointing is discussed also.
基金supported by the National Key Research and Development Program of China under Grant No.2023YFB4502304the National Natural Science Foundation of China under Grant Nos.62272190 and 62302190.
文摘The reliability of high-performance computing(HPC)is essential for program execution stability.However,as the hardware fault rate constantly increases,fault-tolerance techniques such as Checkpoint/Restart(C/R)introduce significant system overhead.This paper proposes Program Error Resilience-Aware Checkpointing Mechanism(ResCheckpointer)to mitigate the overhead of the C/R mechanism.The primary motivation of ResCheckpointer is that we observe that crash proneness(i.e.,the probability of the program crashing after fault occurrence)varies significantly among inter-and intra-HPC programs,which prompts us to flexibly adjust checkpoint intervals for further C/R overhead optimization.Specifically,we first construct the graph neural network(GNN)based learning paradigms to excavate the complex error propagation and effect mechanisms hidden within the HPC program’s execution flow,and propose Crash-Predictor for efficiently predicting programs’crash proneness.Based on this,we build ResCheckpointer,which equips an intelligent checkpoint interval setting strategy for HPC programs,i.e.,denser for the crash proneness stage while sparser for the error resilience stage.Experimental results show that ResCheckpointer can achieve up to 55.37%C/R cost reduction compared with the baseline C/R mechanism.
基金Project supported by the National "863" High-tech Program of China.
文摘Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.
基金the National Natural Science Foundation of China !69673012
文摘A consistent checkpointing algorithm with short freezing time (SFT) is presented in this paper. It supports fault-tolerance in distributed systems. The algorithm has shorter freezing time, lower overhead, and simplicity of recovery. To make checkpoint time shorter, a special control message (Munblock) is used to ensure that a process can respond the checkpoint event quickly at any given time. Moreover, main memory algorithm is used to improve the concurrency of checkpointing. By using SFT, the freezing time resulted by checkpointing is less than 0.03s. Furthermore, the control message number of SFT is only O(n).
文摘In this papert the hard problem of the thorough garbage collection in uncoordinated Checkpointing algorithms is studied. After introduction of the traditional garbage collecting scheme, with which only obsolete checkpoints can be discarded, it is shown that this kind of traditional method may fail to discard any checkpoint in some special cases, and it is necessary and urgent to find a thorough garbage collecting method, with which all the checkpoints useless for any future rollback-recovery including the obsolete ones can be discarded. Then, the Thorough Garbage Collection Theorem is proposed and proved, which ensures the feasibility of the thorough garbage collection, and gives the method to calculate the set of the useful checkpoints as well.
文摘BACKGROUND Chemotherapy with an immune checkpoint inhibitor is one of the standard regimens for treating advanced gastric cancer(AGC).Ascites and peritoneal dissemination are common complications and poor prognostic factors of AGC;however,reports regarding its efficacy and safety in patients with AGC and massive ascites are limited.AIM To evaluate the safety and efficacy of nivolumab combined with chemotherapy in patients with AGC and ascites.METHODS We retrospectively collected clinical data from 124 patients with AGC who received chemotherapy plus nivolumab as first-line treatment from July 2017 to December 2024.Based on computed tomography scans,massive or moderate ascites were classified as high ascites burden(HAB),whereas mild or no ascites were classified as low ascites burden.RESULTS Ascites was detected in 47 patients(38%);26(21%)were classified into the HAB group.Patients in the HAB group exhibited a significantly poorer performance status,a higher prevalence of diffuse-type histology,and lower programmed cell death ligand 1(PD-L1)expression.Combination therapy with FOLFOX and neutropenia was significantly more common in the HAB group.Progression-free survival(PFS)(4.4 months vs 9.3 months,P=0.0012)and overall survival(OS)(7.3 months vs 21.2 months,P<0.0001)were significantly poorer in the HAB group.However,an improvement in ascites was observed in 61.5%of patients in the HAB group.PD-L1 expression did not correlate with either PFS or OS in the HAB group.CONCLUSION Nivolumab plus chemotherapy demonstrated modest efficacy and acceptable toxicity in patients with AGC and HAB.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金the Postdoctoral Science Foundation (No. 20060390461)the Basic Research Foundation of Harbin Engineering University (Nos. HEUF040806,HEUFT05009, and HEUFP05020)
文摘When applied to mobile computing systems,checkpoint protocols for distributed computing systems would face many new challenges, such as low wireless bandwidth, frequent disconnections, and lack of stable storage at mobile hosts. This paper proposes a novel checkpoint protocol to effectively reduce the coordinating overhead. By using a communication vector, only a few processes participate in the checkpointing event. During checkpointing, the scheme can save the time used to trace the dependency tree by sending checkpoint requests to dependent processes at once. In addition, processes are non- blocking in this scheme, since the inconsistency is resolved by the piggyback technique. Hence the unnecessary and orphan messages can be avoided. Compared with the traditional coordinated checkpoint approach, the proposed non-blocking algorithm obtains a minimal number of processes to take checkpoints. It also reduces the checkpoint latency, which brings less overhead to mobile host with limited resources.
基金supported by the NIH/NCI grants(No.P01CA257907)the Educational Department of Hunan Province for Excellent Youth Scholars(No.23B0011)。
文摘In the past decade,immunotherapies targeting cytotoxic T-lymphocyte antigen-4(CTLA-4),programmed cell death 1(PD-1),and PD-1 ligand(PD-L1)have been approved for solid tumors.However,some patients demonstrate suboptimal clinical outcomes due to resistance.The tumor microenvironment(TME)significantly affects the efficiency of immunotherapy by mediating interactions between tumor and non-tumor cells,including dendritic cells,T cells,B cells,macrophages,neutrophils,NK cells,and myeloid-derived suppressor cells(MDSCs).These non-tumor cells often exhibit two phenotypes with altered functions,and tumor cells drives their transition towards tumor promotion through tumor-education.Tumor-educated cells(TECs)are cells influenced by tumor cells,which acquire immune-suppressive phenotypes and promote tumor progression through resistance to anticancer therapies.These cells undergo modifications in response to signals from the tumor,which can influence their roles in tumor progression.Their dynamic interactions with tumor cells contribute to the reshaping of the TME,facilitating cancer growth and immune modulation.This review summarizes research on TECs in TME,explores mechanisms related to tumor education,and discusses their role in tumor progression and immunotherapy resistance.Additionally,potential therapeutic approaches targeting these cells are also reviewed,which may complement current treatment strategies.
基金supported by the National Key Research and Development Program of China(No.2022YFE0102100)the National Natural Science Foundation of China(Nos.U22A20307 and 81930041)。
文摘Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
基金supported by Natural Science Foundation of Guangdong Province,China(2022A1515011575)National Natural Science Foundation of China,China(81873154)President Foundation of Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,China(1202103010)。
文摘Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.
基金supported by Guangdong Basic and Applied Basic Research Foundation(2024A1515012993)the Project of Hunan Provincial Health Commission(No.D202303078877).
文摘Hepatocellular carcinoma(HCC)is a highly aggressive malignancy,largely driven by an immunosuppres-sive tumor microenvironment(TME)that facilitates tumor growth,immune escape,and resistance to therapy.Although immunotherapy—particularly immune checkpoint inhibitors(ICIs)—has transformed the therapeutic landscape by restoring T cell-mediated anti-tumor responses,their clinical benefit as monotherapy remains suboptimal.This limitation is primarily attributed to immunosuppressive components within the TME,including tumor-associated macrophages,regulatory T cells(Tregs),and myeloid-derived suppressor cells(MDSCs).To address these challenges,combination strategies have been explored,such as dual checkpoint blockade targeting programmed cell death protein 1(PD-1),programmed death-ligand 1(PD-L1),and cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),as well as synergistic use of ICIs with anti-angiogenic agents or TME-targeted interventions.These approaches have shown encouraging potential in enhancing immune efficacy.This review outlines the complex crosstalk between the TME and immunotherapeutic responses in HCC,emphasizing how combination regimens may overcome immune resistance.Furthermore,we discuss the remaining hurdles,including therapeutic resistance and immune-related adverse events,and propose future directions involving TME-associated biomarkers and individualized treatment strategies to improve patient outcomes.
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.
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 2021 Key Topic of Qinghai Provincial Health System–Guiding Plan Topic,No.2021-WJZDX-43.
文摘Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.
基金Supported by the National Key Sci-Tech Special Project of China,No.2018ZX10302207the Beijing Natural Science Foundation,No.7222191+3 种基金the Beijing Natural Science Foundation,No.7244426the Fundamental Research Funds for the Central Universities,Peking University,No.PKU2024XGK005the Peking University Medicine Seed Fund for Interdisciplinary Research,No.BMU2021MX007 and No.BMU2022MX001Fundamental Research Funds for the Central Universities,Peking University People’s Hospital Scientific Research Development Funds,No.RDY2020-06 and No.RDJ2022-14.
文摘Hepatocellular carcinoma(HCC)is a primary malignant tumor of the liver and one of the most common malignant tumors,as well as the third leading cause of cancer-related death.In recent years,immune checkpoint inhibitors have emerged as a key strategy in cancer treatment.However,anti-programmed cell death 1/programmed death ligand 1 therapies,one of the main immunotherapeutic approaches,only elicit a response in only approximately 20%of advanced HCC.This suggests that there may be other immune checkpoints playing important roles in HCC immunotherapy.Recent studies have highlighted Signal regulatory protein alpha(SIRPα)is a phagocytic checkpoint in macrophages and other immune cells,as a promising novel therapeutic target in tumor immunotherapy.This review summarizes current progress on SIRPαin HCC and identifies key challenges for future related research.
