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

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 preven...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259945/
https://www.ncbi.nlm.nih.gov/pubmed/32523987
http://dx.doi.org/10.1126/sciadv.aaz3865
Descripción
Sumario: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.

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