In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 6, No. 22 ( 2020-05-29)
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 (T eff ) cells into regulatory T (T reg ) cells, by restricting the expression of T eff cell–intrinsic T reg commitment programs. This was critical for stabilizing T eff cell functions and subverting immune-suppressive signals. T cell–specific deletion of Pcbp1 favored T reg 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 T eff cell functions in cancer immunity.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.aaz3865
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
detail.hit.zdb_id:
2810933-8