Physical or chemical androgen deprivation therapy (ADT) is the cornerstone treatment for metastatic prostate cancer, but relapse eventually occurs and the results of combination of ADT with immunotherapy are disappointing. Here, we show that physical castration can synergize with subsequent immunotherapy while the more commonly used chemical ADT suppresses the immunological protection induced by immunotherapy. Furthermore, chemical ADT can broadly inhibit immune responses. Mechanistically, the inhibition of immune responses by chemical ADT targets T cells by interfering with initial T cell priming, independently of the androgen receptor. We have shown that this off-target immune suppression is mediated by a receptor shared by γ-aminobutyric acid. Further investigation of chemical ADT administered with immunotherapy has revealed that timing and dosing critically control anti-tumor effects. Therefore, this study highlights an underappreciated mechanism of ADT immune suppression and provides a new strategy to enhance immunity and prevent the relapse of advanced prostate cancer.
Citation Format: Yang Pu. Suppression of T cell responses by androgen deprivation drug leads to early relapse. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B043.