Abstract
T Cell Signaling Immunotherapy using antibodies that block the programmed cell death (ligand) 1 [PD-(L)1] or cytotoxic T lymphocyte–associated protein 4 (CTLA-4) immune checkpoint pathways has resulted in impressive responses for some cancer patients. Combined inhibition of both pathways has generally delivered better responses than the targeting of either alone, but how they functionally cross-talk is not well defined. Zhao et al. report that PD-L1 (the main ligand of PD-1) and CD80 (shared ligand for CTLA-4 and the central costimulatory receptor CD28), heterodimerize in cis. Using their model system, the authors found the PD-L1:CD80 cis complexes to be defective in binding either PD-1 or CTLA-4, but the ability of CD80 to activate CD28 appeared to be fully preserved. The interaction of checkpoint pathways might allow opportunities to improve therapy. Immunity 51 , 1059 (2019).
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