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

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Science Advances  29 May 2020:
Vol. 6, no. 22, eaaz3865
DOI: 10.1126/sciadv.aaz3865


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.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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