FcγRIIB expressed on CD8⁺ T cells limits responsiveness to PD-1 checkpoint inhibition in cancer.

ABSTRACT: Checkpoint inhibition using Fc-containing monoclonal antibodies has emerged as a powerful therapeutic approach to augment antitumor immunity. We recently showed that FcγRIIB, the only inhibitory IgG-Fc receptor, is expressed on a population of highly differentiated effector CD8⁺ T cells in the tumors of mice and humans, raising the possibility that CD8⁺ T cell responses may be directly modulated by checkpoint inhibitor binding to T cell-expressed FcγRIIB. Here, we show that despite exhibiting strong proliferative and cytokine responses at baseline, human FcγRIIB^pos CD8⁺ T cells exhibited reduced responsiveness to both PD-1 and CTLA-4 checkpoint inhibition as compared with FcγRIIB^neg CD8⁺ T cells in vitro. Moreover, frequenci

SUBMITTER: Bennion KB 

PROVIDER: S-EPMC11325091 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature