Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses

Abstract Prostate cancer is a significant cause of morbidity and mortality among men worldwide. The cornerstone treatment for metastatic prostate cancer is androgen deprivation, which has known effects on prostate tissue apoptosis and thymic regrowth. These findings, together with interest in developing immune-based treatments for prostate cancer, lead us to question whether androgen deprivation causes changes in the adaptive immune responses of prostate cancer patients, and whether the timing of changes has implications for the sequencing of immunotherapies in combination with androgen deprivation. Peripheral blood mononuclear cells were obtained from patients before beginning androgen deprivation therapy (ADT) and at several time points thereafter. These cells were analyzed for the frequency of specific lymphocyte populations and their response to stimulation. The development of prostate antigen-specific immune responses was assessed using SEREX ( se rological identification of antigens by re combinant ex pression). Patients developed expansion of the naive T-cell compartment persisting over the course of androgen deprivation, together with an increase in effector-cell response to stimulation, and the generation of prostate tissue-associated IgG antibody responses, implying a potential benefit to the use of ADT in combination with prostate cancer-directed immunotherapies. The optimal timing and sequence of androgen deprivation with immune-based therapies awaits future experimental evaluation.