MODULATION OF ANTITUMOR IMMUNE RESPONSE IN MOUSE PROSTATE CANCER MODEL

Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model. We studied their impact on murine prostate cancer cells and on dendritic cells (DC), the most potent antigen-presenting cells known. RM-1 is a murine prostate cancer cell line, resembling hormone-independent model, which is a lethal variant of this disease in humans. Dendritic cells were obtained from murine bone marrow. Cell proliferation assays were performed to evaluate the effect of 5-AzaC and lenalidomide on prostate cancer and DC. Flow cytometry, ELISA and real-time PCR was performed to evaluate the effect of these compounds on DC and prostate cancer cells. 5-AzaC treatment of RM-1 prostate cancer cells and DC resulted in the decreased proliferation for both, while lenalidomide had no effect. DC were treated with lenalidomide and the expression of surface markers MHC Class I, MHC Class II, CD80, CD86, CD 205, and CD40 was increased. Secretion of IL-12 and IL-15 by DC increased significantly with addition of 5-AzaC. There was also the change in the expression of endothelin receptors on DC, which can affect their function. 5-AzaC also resulted in the increased expression of cancer-testis antigen, P1A, by prostate cancer cells. Combination of epigenetic modifications and immunomodulation by 5-AzaC and lenalidomide should increase tumor immunogenicity and it enhanced DC function. Therefore, these compounds might have a role in the treatment of advanced prostate cancer.