Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in c...Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in combating the cancer cells.Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes.Phagocytosis checkpoints,such as CD47,CD24,MHC-I,PD-L1,STC-1 and GD2,have emerged as essential checkpoints for cancer immunotherapy by functioning as“don’t eat me”signals or interacting with“eat me”signals to suppress immune responses.Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy.Genetic ablation of these phagocytosis checkpoints,as well as blockade of their signaling pathways,robustly augments phagocytosis and reduces tumor size.Among all phagocytosis checkpoints,CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment.CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials.However,anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes.Here,we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy,highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.展开更多
Dear Editor,Programmed death ligand-1(PD-L1)is a type 1 transmembrane protein and highly expressed in various cancers that binds to PD-1 on T cells,inhibits T cell activity and proliferation,facilitates cancer cells t...Dear Editor,Programmed death ligand-1(PD-L1)is a type 1 transmembrane protein and highly expressed in various cancers that binds to PD-1 on T cells,inhibits T cell activity and proliferation,facilitates cancer cells to escape T cell-mediated immune surveillance.Immunotherapies by PD-L1/PD-1 blockade have shown effectiveness against different cancer types and revolutionizes cancer treatment in the clinic.However,the response rate to anti-PD-L1/PD-1 antibody remains at about 15-30%as a single agent.1 Thus,there is more to understand regarding the function of PD-L1 in cancer.展开更多
基金the National Natural Science Foundation of China(Nos.31830053,31920103007,8207112072,82122056)the National Key Research and Development Program of China(2020YFA0803201)the Science Technology Commission of Shanghai Municipality(No.20S11900700).
文摘Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in combating the cancer cells.Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes.Phagocytosis checkpoints,such as CD47,CD24,MHC-I,PD-L1,STC-1 and GD2,have emerged as essential checkpoints for cancer immunotherapy by functioning as“don’t eat me”signals or interacting with“eat me”signals to suppress immune responses.Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy.Genetic ablation of these phagocytosis checkpoints,as well as blockade of their signaling pathways,robustly augments phagocytosis and reduces tumor size.Among all phagocytosis checkpoints,CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment.CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials.However,anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes.Here,we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy,highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.
文摘Dear Editor,Programmed death ligand-1(PD-L1)is a type 1 transmembrane protein and highly expressed in various cancers that binds to PD-1 on T cells,inhibits T cell activity and proliferation,facilitates cancer cells to escape T cell-mediated immune surveillance.Immunotherapies by PD-L1/PD-1 blockade have shown effectiveness against different cancer types and revolutionizes cancer treatment in the clinic.However,the response rate to anti-PD-L1/PD-1 antibody remains at about 15-30%as a single agent.1 Thus,there is more to understand regarding the function of PD-L1 in cancer.
