American Federation for Medical Research

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Investigating and Characterizing the Immune Response in Prostate Cancer Treatment
David J. Grossfeld1, Allison B. Reiss1, Lora J. Kasselman1, Heather A. Renna1, Amanda Le Sueur2, Aaron E. Katz2. 1Medicine, NYU Winthrop Hospital, Mineola, New York, United States, 2Urology, NYU Winthrop Hospital, Garden City, New York, United States

Purpose of Study Multiple modalities are available to treat prostate cancer. In humans, cryoablation has shown both immunosuppressive and immunostimulatory results. Combined cryoablation + immunotherapy increased survival and enhanced cytokine, lymphocyte and tumor-specific antibody responses compared to just one of these treatments. Further, radiation therapy can increase output of immunostimulatory cytokines. A more recent prostate cancer treatment, stereotactic body radiation therapy (SBRT), directs high levels of radiation to specific tumor areas using image assistance. In this study, we assess immune response in men after either total prostate cryoablation, focal prostate cryoablation, SBRT via CyberKnife, and radical prostatectomy.
Methods Used In this IRB-approved study, change in cytokine profile, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, -2,-4,-5,-6,-8,-10,-12,-13, IL-2 receptor, CD25+ soluble, interferon (IFN)-γ, are assessed in urine and blood at 3 timepoints: before prostate cancer treatment, immediately after treatment (2 ± 1 week) and 3 months post-treatment. Subjects undergo an Immune Assessment consisting of complete blood count, serum cytokine panel, peripheral blood mononuclear cell isolation, and urine collection at all 3 timepoints. The primary objective is to evaluate post-treatment change in cytokine profile.
Summary of Results For IFN-y, we found a statistical trend with levels in urine stable between visits 2 and 3 for patients 7 and 12, while levels increased for patients 17 and 22 between visits 2 and 3 (p value =.10). Similar patterns were observed with other cytokines such as IL-1β, IL-2, and TNF-α. Although we remain blinded to the treatment modality, patients 7 and 12 were in a group receiving the same treatment while patients 17 and 22 were in a different group receiving the same treatment. Thus, one treatment caused a pattern of changing levels of cytokines in urine between the 2 week and 3 month follow-up immune response assays, while the other treament did not evoke a change.
Conclusions
Physicians have a number of choices in managing prostate cancer and guidance in decision-making is needed to optimize outcomes. Pre- and post-treatment changes in cytokine profile may be a useful indicator of therapeutic response.


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