Deubiquitination and Stabilization of PD-L1 by CSN5

By Seung-Oe Lim, Chia‐Wei Li, W. Xia, Jong-Ho Cha, Li-Chuan Chan, Yun Wu, Shih-Shin Chang, Wan-chi Lin, Jung-Mao Hsu, Yi-Hsin Hsu and 12 more. Cancer Cell, 2016

727 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/3852564d38a11c97ff6bff169c84b4dbc7129a9d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. M. Hung
2. J. Hsu
3. Chia‐Wei Li
4. Jong-Ho Cha
5. Li-Chuan Chan

In Oncology

1. M. Hung
2. J. Hsu
3. Chia‐Wei Li
4. Jong-Ho Cha
5. G. Hortobagyi
6. Li-Chuan Chan

Citations in the corpus

• Mechanisms controlling PD-L1 expression in cancer (2019, background): “IL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion.”
• PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression (2017, methodology): “Multiple signaling pathways, such as STAT, NF-kB, and mTOR, have been reported to regulate PD-L1 expression level (19, 22, 23).”
• HERB: a high-throughput experiment- and reference-guided database of traditional Chinese medicine (2020, background): “For example, curcumin, an active ingredient produced by the Curcuma longa plant, inhibits the COP9 signalosome 5 (CSN5) and diminishes the expression of PD-L1 in cancer cells, which is a well-known target for cancer immune therapies (46).”
• The role of ubiquitination in tumorigenesis and targeted drug discovery (2020, background): “Additionally, COP9 signalosome 5 (CSN5) is required for PD-L1 stabilization by inhibiting its ubiquitination and degradation in cancer cells.(502) However, the specific role of ubiquitination in T cells, macrophages and DC cells is still unclear, especially for immunotherapies targeting ubiquitinati”
• Cyclin D-CDK4 kinase destabilizes PD-L1 via Cul3SPOP to control cancer immune surveillance (2017, neutral): “Although it has been reported that PD-L1 expression can be regulated at both transcriptional 9,10 and post-translational levels 11,12 , it remains unclear whether PD-L1 stability is regulated under physiological conditions such as during cell cycle progression.”