PMID- 27866850 OWN - NLM STAT- MEDLINE DCOM- 20170601 LR - 20220317 IS - 1878-3686 (Electronic) IS - 1535-6108 (Print) IS - 1535-6108 (Linking) VI - 30 IP - 6 DP - 2016 Dec 12 TI - Deubiquitination and Stabilization of PD-L1 by CSN5. PG - 925-939 LID - S1535-6108(16)30497-4 [pii] LID - 10.1016/j.ccell.2016.10.010 [doi] AB - 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-alpha) 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-kappaB p65, is required for TNF-alpha-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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Lim, Seung-Oe AU - Lim SO AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Li, Chia-Wei AU - Li CW AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Xia, Weiya AU - Xia W AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Cha, Jong-Ho AU - Cha JH AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. FAU - Chan, Li-Chuan AU - Chan LC AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030, USA. FAU - Wu, Yun AU - Wu Y AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Chang, Shih-Shin AU - Chang SS AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030, USA. FAU - Lin, Wan-Chi AU - Lin WC AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Hsu, Jung-Mao AU - Hsu JM AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Hsu, Yi-Hsin AU - Hsu YH AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Kim, Taewan AU - Kim T AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Chang, Wei-Chao AU - Chang WC AD - Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan. FAU - Hsu, Jennifer L AU - Hsu JL AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan. FAU - Yamaguchi, Hirohito AU - Yamaguchi H AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Ding, Qingqing AU - Ding Q AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Wang, Yan AU - Wang Y AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Yang, Yi AU - Yang Y AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA. FAU - Chen, Chung-Hsuan AU - Chen CH AD - Genomics Research Center, Academia Sinica, Nankang, 115 Taipei, Taiwan. FAU - Sahin, Aysegul A AU - Sahin AA AD - Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Yu, Dihua AU - Yu D AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030, USA. FAU - Hortobagyi, Gabriel N AU - Hortobagyi GN AD - Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Hung, Mien-Chie AU - Hung MC AD - Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Unit 108, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX 77030, USA; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan. Electronic address: mhung@mdanderson.org. LA - eng GR - 27303C0140/ES/NIEHS NIH HHS/United States GR - P01 CA099031/CA/NCI NIH HHS/United States GR - P30 CA016672/CA/NCI NIH HHS/United States GR - R01 CA109311/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20161117 PL - United States TA - Cancer Cell JT - Cancer cell JID - 101130617 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.- (Peptide Hydrolases) RN - EC 3.4.-.- (COPS5 protein, human) RN - EC 3.4.19.12 (COP9 Signalosome Complex) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - B7-H1 Antigen/chemistry/*metabolism MH - COP9 Signalosome Complex MH - Cell Line, Tumor MH - Curcumin/pharmacology MH - Female MH - Humans MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Mice MH - NF-kappa B/*metabolism MH - Neoplasm Transplantation MH - Neoplasms/*metabolism MH - Peptide Hydrolases/*metabolism MH - Protein Stability MH - Tumor Necrosis Factor-alpha/*metabolism MH - Ubiquitination PMC - PMC5171205 MID - NIHMS834380 OTO - NOTNLM OT - CSN5 OT - PD-L1 OT - TNF-alpha OT - anti-CTLA4 OT - curcumin OT - deubiquitination EDAT- 2016/11/22 06:00 MHDA- 2017/06/02 06:00 PMCR- 2017/12/12 CRDT- 2016/11/22 06:00 PHST- 2016/03/24 00:00 [received] PHST- 2016/07/01 00:00 [revised] PHST- 2016/10/24 00:00 [accepted] PHST- 2016/11/22 06:00 [pubmed] PHST- 2017/06/02 06:00 [medline] PHST- 2016/11/22 06:00 [entrez] PHST- 2017/12/12 00:00 [pmc-release] AID - S1535-6108(16)30497-4 [pii] AID - 10.1016/j.ccell.2016.10.010 [doi] PST - ppublish SO - Cancer Cell. 2016 Dec 12;30(6):925-939. doi: 10.1016/j.ccell.2016.10.010. Epub 2016 Nov 17.