Regulatory T cells modulate immune cells and promote tumor growth in prostatic tumor microenvironment

Abstract Several tumors express antigens that can be recognized by T lymphocytes, suggesting that T cell-mediated immune response may play a critical role in anti-tumor immunity. Studies demonstrated that Regulatory T cells (TR) suppress the functions of immune cells, which are capable to recognized and eliminate tumor cells. However, there exists an utmost demand for further research how immune cells (CD8+ cells, NK cells, etc.) fail to suppress tumor growth and proliferation in the prostatic tumor microenvironment. To investigate this, tumor induction studies in C57/BL-6 mice using transgenic adenocarcinoma of mouse prostate (TRAMP cell lines: -C1, -C2 and -C3) as tumor models were performed. TRAMP-C3 did not form tumor while TRAMP-C1 and TRAMP-C2 cells are tumorigenic. For tumor induction, mice were administered with TRAMP (C1-3) cells. Mice were sacrificed by cervical dislocation when tumor sizes reached ~18–20mm in diameter. A single cell suspension (obtained from spleen, draining lymph node, and tumor) was stained with various cell surface/intracellular immune markers/cytokines to enumerate CD8+ T/TR/NK/Ly6G/Ly6C+ -MDSC cells. Additionally, the expression of TGF-β, IFN-γ, IL-4, IL-17, PD-1 and PDL-1 and cell cycle analysis for CD8+ T cells was also carried out. Our findings suggest that recruitment of suppressive TR and Ly6G/Ly6C+ -MDSC cells and high expression TGF-β and PD-1 and lower expression of NKG2D and IFN-γ and low number of NK and CD8+ cytotoxic T cells in spleen, draining LN and tumor of TRAMP-C1 and TRAMP-C2 (as compared to TRAMP-C3 mice) facilitated tumor growth. Therefore, the expression of PD-1 and TGF-β on TR suggest that TR might be playing a significant role in facilitating tumor growth and progression.