CBX7 represses the POU2F2 to inhibit the PD-L1 expression and regulate the immune response in bladder cancer

Weigang Ren; Jiannan Ren; Naiwen Zhang; Xinlin Liu; Yao Deng; Yanyan Jiang; Bin Yan; Xiaoxiong Xiao; Haixin Yu

doi:10.1016/j.bbrc.2022.04.114

CBX7 represses the POU2F2 to inhibit the PD-L1 expression and regulate the immune response in bladder cancer

Biochem Biophys Res Commun. 2022 Jul 12:613:12-18. doi: 10.1016/j.bbrc.2022.04.114. Epub 2022 Apr 28.

Authors

Weigang Ren¹, Jiannan Ren², Naiwen Zhang³, Xinlin Liu³, Yao Deng³, Yanyan Jiang³, Bin Yan⁴, Xiaoxiong Xiao⁵, Haixin Yu⁶

Affiliations

¹ Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410005, China.
² Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China.
³ Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
⁴ Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China. Electronic address: bin.yan01@csu.edu.cn.
⁵ Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: xiaoxx1988@csu.edu.cn.
⁶ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address: haixin.y@outlook.com.

PMID: 35526483
DOI: 10.1016/j.bbrc.2022.04.114

Abstract

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system worldwide. To date, immune checkpoint inhibitors (including PD-1/PD-L1) have been applied to treat patients with bladder cancer in the clinic and achieved the promising outcome. Further improvement of the anticancer efficiency of these immune therapies is crucial for bladder cancer. Our previous RNA-seq data on CBX7 (GSE185630) suggested that CBX7 might repress PD-L1 expression and PD-1 checkpoint pathway in cancer. In this study, we revealed that CBX7 downregulated the expression of POU2F2 that indirectly repressed the PD-L1 in BC cells. Depletion of CBX7 resulted in resistance to PD-1 blockade in bladder cancer. Collectively, our results suggested that the CBX7/POU2F2/PD-L1 axis plays an important role in determining the antitumor effect of PD-1 blockade in bladder cancer.

Keywords: Bladder cancer; CBX7; PD-L1; POU2F2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen* / antagonists & inhibitors
B7-H1 Antigen* / immunology
B7-H1 Antigen* / metabolism
Humans
Immune Checkpoint Inhibitors / pharmacology
Octamer Transcription Factor-2* / immunology
Polycomb Repressive Complex 1* / immunology
Programmed Cell Death 1 Receptor / immunology
Urinary Bladder Neoplasms* / immunology
Urinary Bladder Neoplasms* / pathology

Substances

B7-H1 Antigen
CBX7 protein, human
CD274 protein, human
Immune Checkpoint Inhibitors
Octamer Transcription Factor-2
PDCD1 protein, human
POU2F2 protein, human
Programmed Cell Death 1 Receptor
Polycomb Repressive Complex 1