Androgen receptor antagonists compromise T cell response against prostate cancer leading to early tumor relapse

Surgical and medical androgen deprivation therapy (ADT) is a cornerstone for prostate cancer treatment, but relapse usually occurs. We herein show that orchiectomy synergizes with immunotherapy, whereas the more widely used treatment of medical ADT involving androgen receptor (AR) antagonists suppresses immunotherapy.

Furthermore, we observed that the use of medical ADT could unexpectedly impair the adaptive immune responses through interference with initial T cell priming rather than in the reactivation or expansion phases. Mechanistically, we have revealed that inadvertent immunosuppression might be potentially mediated by a receptor shared with γ-aminobutyric acid. Our data demonstrate that the timing and dosing of antiandrogens are critical to maximizing the antitumor effects of combination therapy. This study highlights an underappreciated mechanism of AR antagonist-mediated immunosuppression and provides a new strategy to enhance immune response and prevent the relapse of advanced prostate cancer.

Science translational medicine. 2016 Apr 06 [Epub]

Yang Pu, Meng Xu, Yong Liang, Kaiting Yang, Yajun Guo, Xuanming Yang, Yang-Xin Fu

School of Bioscience and Bioengineering, South China University of Technology (SCUT), Guangzhou 510006, China. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA., Department of Pathology, University of Chicago, Chicago, IL 60637, USA., IBP-UTSW Joint Immunotherapy Group, Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., IBP-UTSW Joint Immunotherapy Group, Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China., School of Bioscience and Bioengineering, South China University of Technology (SCUT), Guangzhou 510006, China., School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. Department of Pathology, University of Chicago, Chicago, IL 60637, USA. IBP-UTSW Joint Immunotherapy Group, Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. 

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