期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 8, 期 333, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aad5659
关键词
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资金
- NIH [CA134563]
- National 12.5 Major Project of China [2012ZX10001006002004]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning [TP2015013]
- Shanghai Pujiang Program
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 gamma-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.
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