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Review
. 2017 Dec;24(12):T297-T310.
doi: 10.1530/ERC-17-0145. Epub 2017 Aug 16.

Androgen Deprivation and Immunotherapy for the Treatment of Prostate Cancer

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Free PMC article
Review

Androgen Deprivation and Immunotherapy for the Treatment of Prostate Cancer

Melissa Gamat et al. Endocr Relat Cancer. .
Free PMC article

Abstract

Prostate cancer is the most common newly diagnosed malignancy in men, and the second most common cause of cancer-related death in the United States. The primary treatment for recurrent prostate cancer is androgen deprivation, and this therapy is typically continued lifelong for patients with metastatic prostate cancer. Androgens and androgen deprivation have profound effects on the immune system, a finding that has become more appreciated in an era where immune-based treatments for cancer are being increasingly explored. Preclinical studies suggest that androgen deprivation could potentially positively or negatively affect the use of approved immunotherapies, or those that are being developed for the treatment of prostate cancer. In this review, we provide a brief overview of the different types of androgen deprivation treatments used in the management of prostate cancer, discuss their effects on prostate tumors and the immune system and how they are being explored in combination with immunotherapy. Finally, we address some of the critical questions in the field that must be answered to identify the best approaches to combine androgen deprivation with immunotherapy for the treatment of prostate cancer.

Keywords: androgen deprivation; immunotherapy; prostate cancer; vaccine.

Conflict of interest statement

Conflicts of Interest: DGM has ownership interest, has received research support, and serves as consultant to Madison Vaccines, Inc. MG has no relevant potential conflicts of interest.

Figures

Figure 1
Figure 1
Sex steroids have effects on both the prostate and the thymus. Androgens such as testosterone and DHT induces a decrease in thymus weight and an increase in prostate weight. Conversely, androgen deprivation causes an increase in thymus weight and a decrease in prostate weight. Androgens also affect T cells, with testosterone causing an increase in immunosuppressive Tregs and IL-10 production and DHT causing a decrease in IFNγ-secretion by T cells. In addition, estrogen causes an increase in Tregs and increased β2-macroglobulin expression and MHC molecules. Androgen deprivation causes an increase in naïve T cell numbers, increase in antigen-specific T cells and increased IFNγ production as well as causing T-cell infiltration into the prostate.

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