The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases.Recent basic and clinical studies have revealed novel biology of the ...The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases.Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy.In this review,we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways,PD-1/PD-L1 and B7-H3 as metabolic regulators,the glycobiology of PD-1/PD-L1,B7x(B7-H4)and B7-H3,and the recently characterized PD-L1/B7-1 cis-interaction.We also cover the tumor-intrinsic and-extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings.Finally,we review new immunotherapies targeting B7-H3,B7x,PD-1/PD-L1,and CTLA-4 in current clinical trials.展开更多
基金NIH R01CA175495 and R01CA262132the Department of Defense(PC210331 and BC190403)the Price Family Foundation.M.C.P.is supported by NIH 5TL1TR002557.A.T.M.is supported by Scandinavia/Borge.
文摘The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases.Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy.In this review,we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways,PD-1/PD-L1 and B7-H3 as metabolic regulators,the glycobiology of PD-1/PD-L1,B7x(B7-H4)and B7-H3,and the recently characterized PD-L1/B7-1 cis-interaction.We also cover the tumor-intrinsic and-extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings.Finally,we review new immunotherapies targeting B7-H3,B7x,PD-1/PD-L1,and CTLA-4 in current clinical trials.
