2. Academic Validation
  3. Androgen receptor transcriptionally inhibits programmed death ligand-1 (PD-L1) expression and influences immune escape in bladder cancer

Androgen receptor transcriptionally inhibits programmed death ligand-1 (PD-L1) expression and influences immune escape in bladder cancer

  • Lab Invest. 2023 Apr 12;100148. doi: 10.1016/j.labinv.2023.100148.
Anran Sun 1,  Yu Luo 2,  Wen Xiao 3,  Zhipeng Zhu 4,  Hongyu Yan 4,  Chaohao Miao 2,  Wenzhao Zhang 5,  Peide Bai 2,  Chenfeng Liu 6,  Dianqiang Yang 6,  Zhiqiang Shao 7,  Jing Song 7,  Zhun Wu 2,  Bin Chen 8,  Jinchun Xing 9,  Tao Wang 10
Affiliations

Affiliations

  • 1 The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China; Oncology Research Center, Foresea Life Insurance Guangzhou General Hospital, Guangzhou, Guangdong, China.
  • 2 The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China.
  • 3 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 School of Medicine, Xiamen University, Xiang'an, Xiamen, China.
  • 5 The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
  • 6 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiang'an, Xiamen, China.
  • 7 Xiamen University Laboratory Animal Center, Xiamen University, Xiang'an, Xiamen, China.
  • 8 The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China. Electronic address: chenbin5557@163.com.
  • 9 The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China. Electronic address: xmcua2007@sina.com.
  • 10 The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China. Electronic address: taowang@xmu.edu.cn.
PMID: 37059268 DOI: 10.1016/j.labinv.2023.100148
Abstract

In multiple clinical trials, Immune Checkpoint blockade-based immunotherapy has shown significant therapeutic efficacy in bladder Cancer (BCa). Sex is closely related to the incidence rate and prognosis of BCa. As one of the sex hormone receptors, the Androgen Receptor (AR) is a well-known key regulator that promotes the progression of BCa. However, the regulatory mechanism of AR in the immune response of BCa is still unclear. In this study, the expression of AR and programmed cell death-ligand 1 (PD-L1) was negatively correlated in BCa cells, clinical tissues, and tumor data extracted from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA) cohort. A human BCa cell line was transfected to alter expression of AR. The results show that AR negatively regulated PD-L1 expression by directly binding to AR response elements (AREs) on the PD-L1 promoter region. In addition, AR overexpression in BCa cells significantly enhanced the antitumor activity of co-cultured CD8+ T cells. Injection of anti-PD-L1 monoclonal Antibodies into C3H/HeN mice significantly suppressed tumor growth, and stable expression of AR dramatically enhanced the antitumor activity in vivo. In conclusion, this study describes a novel role of AR in regulating the immune response to BCa by targeting PD-L1, thus providing potential therapeutic strategies for immunotherapy in BCa.

Keywords

androgen receptor; bladder cancer; immune surveillance; programmed cell death ligand 1; tumor immunotherapy.

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