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

ABSTRACT: 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.

SUBMITTER: Ansa-Addo EA 

PROVIDER: S-EPMC7259945 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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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 (T<sub>eff</sub>) cells into regulatory T (T<sub>reg</sub>) cells, by restricting the expression of T<sub>eff</sub> cell-intrinsic T<sub>reg</sub> commitment programs. This  ...[more]

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