Author: Ansa-Addo, Ephraim A; Huang, Huai-Cheng; Riesenberg, Brian; Iamsawat, Supinya; Borucki, Davis; Nelson, Michelle H; Nam, Jin Hyun; Chung, Dongjun; Paulos, Chrystal M; Liu, Bei; Yu, Xue-Zhong; Philpott, Caroline; Howe, Philip H; Li, Zihai
Title: RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity. Cord-id: 3bhihnlu Document date: 2020_5_1
ID: 3bhihnlu
Snippet: 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 (Teff) cells into regulatory T (Treg) cells, by restricting the expression of Teff cell-intrinsic Treg commitment programs. This was critical for stabilizing Teff cell funct
Document: 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 (Teff) cells into regulatory T (Treg) cells, by restricting the expression of Teff cell-intrinsic Treg commitment programs. This was critical for stabilizing Teff cell functions and subverting immune-suppressive signals. T cell-specific deletion of Pcbp1 favored Treg 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 Teff cell functions in cancer immunity.
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