Nature Communications (Mar 2022)
USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy
- Wenjun Xiong,
- Xueliang Gao,
- Tiantian Zhang,
- Baishan Jiang,
- Ming-Ming Hu,
- Xia Bu,
- Yang Gao,
- Lin-Zhou Zhang,
- Bo-Lin Xiao,
- Chuan He,
- Yishuang Sun,
- Haiou Li,
- Jie Shi,
- Xiangling Xiao,
- Bolin Xiang,
- Conghua Xie,
- Gang Chen,
- Haojian Zhang,
- Wenyi Wei,
- Gordon J. Freeman,
- Hong-Bing Shu,
- Haizhen Wang,
- Jinfang Zhang
Affiliations
- Wenjun Xiong
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Xueliang Gao
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina
- Tiantian Zhang
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Baishan Jiang
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Ming-Ming Hu
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Xia Bu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
- Yang Gao
- Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University
- Lin-Zhou Zhang
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Bo-Lin Xiao
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Chuan He
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Yishuang Sun
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Haiou Li
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Jie Shi
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Xiangling Xiao
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Bolin Xiang
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Conghua Xie
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- Gang Chen
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Haojian Zhang
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Wenyi Wei
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School
- Gordon J. Freeman
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
- Hong-Bing Shu
- Frontier Science Center for Immunology and Metabolism, Medical Research Institute, School of Medicine, Wuhan University
- Haizhen Wang
- Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina
- Jinfang Zhang
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University
- DOI
- https://doi.org/10.1038/s41467-022-29401-6
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
The regulatory mechanisms of PD-L1 posttranslational modifications are not completely understood. Here the authors show that USP8 negatively regulates PD-L1 protein abundance by removing the K63-linked ubiquitination of PD-L1; while USP8 inhibition increases MHC-I expression and triggers anti-tumour immune responses through activating NF-κB signalling.
