免疫系统
癌症研究
生物
免疫原性
免疫疗法
免疫佐剂
脱氮酶
癌症免疫疗法
免疫原性细胞死亡
癌症
泛素
免疫学
生物化学
基因
遗传学
作者
Xing Huang,Qi Zhang,Yiting Lou,Junli Wang,Xinyu Zhao,Lin Wang,Xiaozhen Zhang,Shanshan Li,Yulan Zhao,Qi Chen,Xueli Bai
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2019-10-01
卷期号:7 (10): 1580-1590
被引量:92
标识
DOI:10.1158/2326-6066.cir-18-0910
摘要
Abstract PD-1 (CD279)–PD-L1 (CD274) inhibitory signaling is critical for cancer immune evasion, and thus has become one of the major targets in anticancer immunotherapy. There are several studies that demonstrate the potent effects of posttranslational modifications of CD274 on immune inactivation and suppression, such as ubiquitination, phosphorylation, glycosylation, and palmitoylation. However, the regulatory mechanisms for CD274 deubiquitination are still largely unclear. Here, we identified ubiquitin-specific protease 22 (USP22) as a novel deubiquitinase of CD274. USP22 directly interacted with the C terminus of CD274, inducing its deubiquitination and stabilization. Across multiple cancer types, USP22 was highly expressed and frequently altered in liver cancer, closely correlating with poor prognosis of these patients. Genetic depletion of USP22 inhibited liver cancer growth in an immune system–dependent manner, increased tumor immunogenicity and tumor-infiltrating lymphocytes, and improved therapeutic efficacy of CD274-targeted immunotherapy and CDDP-based chemotherapy in mice. We demonstrate that targeting USP22 is a promising strategy to potentiate anticancer immunity for CD274-amplified cancer.
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