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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.

SUBMITTER: Lim SO

PROVIDER: S-EPMC5171205 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Deubiquitination and Stabilization of PD-L1 by CSN5.

Lim Seung-Oe SO Li Chia-Wei CW Xia Weiya W Cha Jong-Ho JH Chan Li-Chuan LC Wu Yun Y Chang Shih-Shin SS Lin Wan-Chi WC Hsu Jung-Mao JM Hsu Yi-Hsin YH Kim Taewan T Chang Wei-Chao WC Hsu Jennifer L JL Yamaguchi Hirohito H Ding Qingqing Q Wang Yan Y Yang Yi Y Chen Chung-Hsuan CH Sahin Aysegul A AA Yu Dihua D Hortobagyi Gabriel N GN Hung Mien-Chie MC

Cancer cell 20161117 6

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. ...[more]

PMID: 27866850

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