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

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

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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 g-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.

Original languageEnglish (US)
Article numberra47
JournalScience Translational Medicine
Volume8
Issue number333
DOIs
StatePublished - Apr 6 2016

ASJC Scopus subject areas

  • Medicine(all)

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