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

被引：35

作者：

Ansa-Addo, Ephraim A. ^{[1
,2
,3
,4
]}

Huang, Huai-Cheng ^{[1
,2
,5
]}

Riesenberg, Brian ^{[1
,2
,3
,4
]}

Iamaswat, Supinya ^{[1
,2
]}

Borucki, Davis ^{[1
,2
]}

Nelson, Michelle H. ^{[1
,2
]}

Nam, Jin Hyun ^{[6
]}

Chung, Dongjun ^{[3
,4
,6
,9
]}

Paulos, Chrystal M. ^{[1
,2
,10
,11
]}

Liu, Bei ^{[1
,2
]}

Yu, Xue-Zhong ^{[1
,2
]}

Philpott, Caroline ^{[7
]}

Howe, Philip H. ^{[8
]}

Li, Zihai ^{[1
,2
,3
,4
]}

机构：

[1] Med Univ South Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA

[2] Med Univ South Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA

[3] Ohio State Univ, Comprehens Canc Ctr James, Pelotonia Inst Immunooncol, Columbus, OH 43210 USA

[4] Ohio State Univ, Comprehens Canc Ctr James, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA

[5] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, 7 Chung San South Rd, Taipei 10002, Taiwan

[6] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA

[7] NIDDK, Genet & Metab Sect, Liver Dis Branch, Bethesda, MD 20892 USA

[8] Med Univ South Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA

[9] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA

[10] Emory Univ, Winship Canc Inst, Sch Med, Dept Surg, Atlanta, GA 30322 USA

[11] Emory Univ, Winship Canc Inst, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 22期

关键词：

TRANSCRIPTION FACTOR; ANTITUMOR IMMUNITY; EXPRESSION; THERAPY; PHOSPHORYLATION; CHAPERONE; PROGRAMS; ZFP36L1; COMPLEX; PD-1;

D O I：

10.1126/sciadv.aaz3865

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

共 58 条

[1] Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer [J].