Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, howev...Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.展开更多
Inhibitory checkpoint molecules include programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),cytotoxic T lymphocyte antigen-4(CTLA-4),human endogenous retrovirus-H Long terminal repeat-associating 2(HHL...Inhibitory checkpoint molecules include programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),cytotoxic T lymphocyte antigen-4(CTLA-4),human endogenous retrovirus-H Long terminal repeat-associating 2(HHLA2),B7 homolog 4 protein(B7-H4),T cell membrane protein-3(TIM-3)and Lymphocyte-activation gene 3(LAG-3),which are up-regulated during tumorigenesis.These pathways are essential to down-regulate the immune system by blocking the activation of T cells.In recent years,immune checkpoint blockers(ICBs)against PD-1,PD-L1,CTLA-4 or TIM-3 has made remarkable progress in the clinical application,revolutionizing the treatment of malignant tumors and improving patients’overall survival.However,the efficacy of ICBs in some patients does not seem to be good enough,and more immune-related adverse events(irAEs)will inevitably occur.Therefore,biomarkers research provides practical guidance for clinicians to identify patients who are most likely to benefit from or exhibit resistance to particular types of immune checkpoint therapy.There are two points in general.On the one hand,given the spatial and temporal differential expression of immune checkpoint molecules during immunosuppression process,it is essential to understand their mechanisms to design the most effective individualized therapy.On the other hand,due to the lack of potent immune checkpoints,it is necessary to combine them with novel biomarkers(such as exosomes and ctDNA)and other anticancer modalities(such as chemotherapy and radiotherapy).展开更多
基金This study was supported in part by National Natural Science Foundation of China(No. 81802255)Young Talents in Shanghai(No. 2019 QNBJ)+2 种基金"Dream Tutor" Outstanding Young Talents Program(No. fkyq1901)Clinical Research Project of Shanghai Pulmonary Hospital(No. fk18005)Key Discipline in 2019 (oncology), Project of Shanghai Municipal Science and Technology Commission (Project of Municipal Science and Technology Commission), and Scientific Research Project of Shanghai Pulmonary Hospital(No. fkcx1903)。
文摘Immunotherapy that targets checkpoints, especially programmed cell death protein 1 and programmed cell death ligand 1, has revolutionized cancer therapy regimens. The overall response rate to mono-immunotherapy, however, is limited, emphasizing the need to potentiate the efficacy of these regimens. The functions of immune cells are modulated by multiple stimulatory and inhibitory molecules, including lymphocyte activation gene 3 (LAG-3). LAG-3 is co-expressed together with other inhibitory checkpoints and plays key roles in immune suppression. Increasing evidence, particularly in the last 5 years, has shown the potential of LAG-3 blockade in anti-tumor immunity. This review provides an update on the biological properties and clinical applications of LAG-3 in cancers.
基金the National Natural Science Foundation of China(81872200,31900558)the Natural Science Foundation of Hubei Province(2018CFB510)+1 种基金the Zhongnan Hospital of Wuhan University Science,Technology and Innovation Seed Fund(CXPY2017029)the Fundamental Research Funds for the Central Universities(2042018kf0091).
文摘Inhibitory checkpoint molecules include programmed cell death-1(PD-1),programmed cell death ligand-1(PD-L1),cytotoxic T lymphocyte antigen-4(CTLA-4),human endogenous retrovirus-H Long terminal repeat-associating 2(HHLA2),B7 homolog 4 protein(B7-H4),T cell membrane protein-3(TIM-3)and Lymphocyte-activation gene 3(LAG-3),which are up-regulated during tumorigenesis.These pathways are essential to down-regulate the immune system by blocking the activation of T cells.In recent years,immune checkpoint blockers(ICBs)against PD-1,PD-L1,CTLA-4 or TIM-3 has made remarkable progress in the clinical application,revolutionizing the treatment of malignant tumors and improving patients’overall survival.However,the efficacy of ICBs in some patients does not seem to be good enough,and more immune-related adverse events(irAEs)will inevitably occur.Therefore,biomarkers research provides practical guidance for clinicians to identify patients who are most likely to benefit from or exhibit resistance to particular types of immune checkpoint therapy.There are two points in general.On the one hand,given the spatial and temporal differential expression of immune checkpoint molecules during immunosuppression process,it is essential to understand their mechanisms to design the most effective individualized therapy.On the other hand,due to the lack of potent immune checkpoints,it is necessary to combine them with novel biomarkers(such as exosomes and ctDNA)and other anticancer modalities(such as chemotherapy and radiotherapy).
