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Deubiquitination and Stabilization of PD-L1 by CSN5.

Abstract：

:Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Lim SO,Li CW,Xia W,Cha JH,Chan LC,Wu Y,Chang SS,Lin WC,Hsu JM,Hsu YH,Kim T,Chang WC,Hsu JL,Yamaguchi H,Ding Q,Wang Y,Yang Y,Chen CH,Sahin AA,Yu D,Hortobagyi GN,Hung MC

doi

10.1016/j.ccell.2016.10.010

subject

Has Abstract

pub_date

2016-12-12 00:00:00

pages

925-939

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(16)30497-4

journal_volume

30

pub_type

杂志文章

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