ABSTRACT
BACKGROUND: The purpose of this study was to investigate the immunological impact of combining neoadjuvant total androgen suppression (TAS) with radiotherapy (xRT) in the treatment of prostate cancer by monitoring blood cytokine levels. PATIENTS AND METHODS: Participants were stage I-II prostate cancer patients receiving xRT alone (n=18) or TAS+xRT (n=19) under the procedures outlined in RTOG protocols #94-08 and #94-13. Peripheral blood samples were collected immediately prior to TAS (xRT+TAS group), immediately prior to xRT, 24 hours after initiation of xRT, and weekly during xRT. Samples were monitored for the immunoregulatory cytokines interleukin (IL)-1beta, IL-6 and transforming growth factor (TGF)beta using ELISA procedures. RESULTS: Following initiation of xRT, both patient groups demonstrated an immediate elevation of the proinflammatory cytokines IL-1beta and IL-6 in their plasma. These cytokine levels appeared to peak after 1-2 weeks of xRT before returning toward pre xRT levels. In contrast, the profibrotic cytokine TGFbeta appeared to decrease immediately following initiation of xRT, but, subsequently, underwent two distinct waves of elevation, occurring at 1-2 weeks and 5-6 weeks into the xRT. Surprisingly, while the temporal pattern of plasma cytokine response was similar in both treatment groups, the magnitude of cytokine expression was noticeably different, appearing to be significantly affected by the addition of TAS. Indeed, administration of neoadjuvant TAS appeared to bring about a marked elevation of IL-1beta and IL-6 and a significant reduction in TGFbeta when compared to patients receiving xRT alone. CONCLUSION: The precise mechanisms underlying this TAS-related increase of the proinflammatory cytokines IL-1beta and IL-6 and decrease of the profibrotic cytokine TGFbeta remain unclear. However, previous reports have documented that androgens tend to be immunosuppressive in nature. It is conceivable, therefore, that administration of TAS shifts the ratio of proinflammatory and profibrotic cytokines toward a more immunostimulatory state.
Subject(s)
Adenocarcinoma/blood , Androgen Antagonists/administration & dosage , Antineoplastic Agents, Hormonal/administration & dosage , Cytokines/blood , Prostatic Neoplasms/blood , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Aged , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Radiotherapy, AdjuvantABSTRACT
BACKGROUND: This study sought to better define the immunological impact of combining neoadjuvant total androgen suppression (TAS) with radiotherapy (xRT) in treating prostate cancer. MATERIALS AND METHODS: Subjects selected (n = 37) were stage I-II prostate cancer patients meeting the eligibility requirements for RTOG protocols 94-08 or 94-13. Flow cytometric monitoring of circulating T helper (Th), T suppressor/cytotoxic (Ts), natural killer (NK) and B lymphocytes was performed weekly. RESULTS: Significant reduction of all lymphocyte subsets occurred as a result of xRT. Comparison between treatment groups demonstrated that the B lymphocyte and NK lymphocyte radioresponse was not influenced by TAS, but the Th and Ts lymphocyte response was, with addition of TAS leading to less radiation-induced decline. CONCLUSION: The basis for this T cell response is unclear, but may involve a TAS-induced reduction of testosterone's immunomodulation of T cell proliferation and apoptosis and/or a direct, TAS-induced thymic stimulation. Our data suggest that addition of TAS to xRT appears to have no detrimental effects on lymphocyte subsets, and, indeed, may have favorable effects on T cells.
