Proceedings of the National Academy of Sciences · 2023 · 37 citations · 63 references
Life SciencesImmunologyOncologyCancer ImmunologyImmunotherapyTumor ImmunologyAntigen RecognitionAntitumor T Cell ResponsesCancer ImmunotherapyCytotoxic T Lymphocyte ResponsesImmune Checkpoint RegulationT Cell Responses To TumorsAdaptive Antitumor ImmunityAntigen Presenting CellsCd8 Positive T Cell ResponsesCd80 InteractionsCtla-4 SignalingPd-l1 BlockadeProgrammed Cell Death Protein 1 (Pd-1) PathwayT-cell Responses To Tumor Antigens
PD-L1 has two receptors: PD-1 and CD80. Previous reports assumed that PD-L1 and CD80 interacted in trans, but recent reports showed that only cis PD-L1/CD80 interactions existed, and prevention of cis PD-L1/CD80 interactions on antigen-presenting cells (APCs) reduced antitumor immunity via augmenting PD-L1/PD-1 and CD80/CTLA4 interactions between T and APCs. Here, using tumor-bearing mice capable of cis and trans or trans only PD-L1/CD80 interactions, we show that trans PD-L1/CD80 interactions do exist between tumor and T cells, and the effects of trans PD-L1/CD80 interactions require tumor cell expression of MHC-I and T cell expression of CD28. The blockade of PD-L1/CD80 interactions in mice with both cis and trans interactions or with only trans interactions augments antitumor immunity by expanding IFN-γ–producing CD8 + T cells and IFN-γ–dependent NOS2-expressing tumor-associated macrophages. Our studies indicate that although cis and trans PD-L1/CD80 interactions may have opposite effects on antitumor immunity, the net effect of blocking PD-L1/CD80 interactions in vivo augments CD8 + T cell-mediated antitumor immunity.
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