RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity

摘要

Distinct lineages of T cells can act in response to various environmental cues to either drive or restrict immune-mediated pathology. Here, we identify the RNA binding protein, poly(C)-binding protein 1 (PCBP1) as an intracellular immune checkpoint that is up-regulated in activated T cells to prevent conversion of effector T (Tsubeff/sub) cells into regulatory T (Tsubreg/sub) cells, by restricting the expression of Tsubeff/sub cell–intrinsic Tsubreg/sub commitment programs. This was critical for stabilizing Tsubeff/sub cell functions and subverting immune-suppressive signals. T cell–specific deletion of Pcbp1 favored Tsubreg/sub cell differentiation, enlisted multiple inhibitory immune checkpoint molecules including PD-1, TIGIT, and VISTA on tumor-infiltrating lymphocytes, and blunted antitumor immunity. Our results demonstrate a critical role for PCBP1 as an intracellular immune checkpoint for maintaining Tsubeff/sub cell functions in cancer immunity.