Deubiquitination and Stabilization of PD-L1 by CSN5

Seung Oe Lim; Chia Wei Li; Weiya Xia; Jong Ho Cha; Li Chuan Chan; Yun Wu; Shih Shin Chang; Wan Chi Lin; Jung Mao Hsu; Yi Hsin Hsu; Taewan Kim; Wei Chao Chang; Jennifer L. Hsu; Hirohito Yamaguchi; Qingqing Ding; Yan Wang; Yi Yang; Chung Hsuan Chen; Aysegul A. Sahin; Dihua Yu; Gabriel N. Hortobagyi; Mien Chie Hung

doi:10.1016/j.ccell.2016.10.010

Deubiquitination and Stabilization of PD-L1 by CSN5

Seung Oe Lim, Chia Wei Li, Weiya Xia, Jong Ho Cha, Li Chuan Chan, Yun Wu, Shih Shin Chang, Wan Chi Lin, Jung Mao Hsu, Yi Hsin Hsu, Taewan Kim, Wei Chao Chang, Jennifer L. Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Yi Yang, Chung Hsuan Chen, Aysegul A. Sahin, Dihua YuGabriel N. Hortobagyi, Mien Chie Hung

Research output: Contribution to journal › Article › peer-review

521 Scopus citations

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.

Original language	English (US)
Pages (from-to)	925-939
Number of pages	15
Journal	Cancer cell
Volume	30
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2016.10.010
State	Published - Dec 12 2016

Keywords

CSN5
PD-L1
TNF-α
anti-CTLA4
curcumin
deubiquitination

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Flow Cytometry and Cellular Imaging Facility
Functional Genomics Core
Research Animal Support Facility
Tissue Biospecimen and Pathology Resource
Cytogenetics and Cell Authentication Core

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10.1016/j.ccell.2016.10.010

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Lim, S. O., Li, C. W., Xia, W., Cha, J. H., Chan, L. C., Wu, Y., Chang, S. S., Lin, W. C., Hsu, J. M., Hsu, Y. H., Kim, T., Chang, W. C., Hsu, J. L., Yamaguchi, H., Ding, Q., Wang, Y., Yang, Y., Chen, C. H., Sahin, A. A., ... Hung, M. C. (2016). Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer cell, 30(6), 925-939. https://doi.org/10.1016/j.ccell.2016.10.010

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title = "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.",

keywords = "CSN5, PD-L1, TNF-α, anti-CTLA4, curcumin, deubiquitination",

author = "Lim, {Seung Oe} and Li, {Chia Wei} and Weiya Xia and Cha, {Jong Ho} and Chan, {Li Chuan} and Yun Wu and Chang, {Shih Shin} and Lin, {Wan Chi} and Hsu, {Jung Mao} and Hsu, {Yi Hsin} and Taewan Kim and Chang, {Wei Chao} and Hsu, {Jennifer L.} and Hirohito Yamaguchi and Qingqing Ding and Yan Wang and Yi Yang and Chen, {Chung Hsuan} and Sahin, {Aysegul A.} and Dihua Yu and Hortobagyi, {Gabriel N.} and Hung, {Mien Chie}",

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year = "2016",

month = dec,

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doi = "10.1016/j.ccell.2016.10.010",

language = "English (US)",

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T1 - Deubiquitination and Stabilization of PD-L1 by CSN5

AU - Lim, Seung Oe

AU - Li, Chia Wei

AU - Xia, Weiya

AU - Cha, Jong Ho

AU - Chan, Li Chuan

AU - Wu, Yun

AU - Chang, Shih Shin

AU - Lin, Wan Chi

AU - Hsu, Jung Mao

AU - Hsu, Yi Hsin

AU - Kim, Taewan

AU - Chang, Wei Chao

AU - Hsu, Jennifer L.

AU - Yamaguchi, Hirohito

AU - Ding, Qingqing

AU - Wang, Yan

AU - Yang, Yi

AU - Chen, Chung Hsuan

AU - Sahin, Aysegul A.

AU - Yu, Dihua

AU - Hortobagyi, Gabriel N.

AU - Hung, Mien Chie

PY - 2016/12/12

Y1 - 2016/12/12

N2 - 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.

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-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.

KW - CSN5

KW - PD-L1

KW - TNF-α

KW - anti-CTLA4

KW - curcumin

KW - deubiquitination

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JO - Cancer cell

JF - Cancer cell

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Deubiquitination and Stabilization of PD-L1 by CSN5

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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