PD-1 expression on Foxp3+ Treg cells modulates CD8+ T cell function in prostatic tumor microenvironment

Abstract

Abstract Regulatory T (Treg) cells act as terminators of T cell immune response during prostate cancer progression and development. However, their role and immunosuppressive mechanism(s) in context to programmed death 1 (PD-1) is not completely understood. The present investigation is aimed to determine the role of PD-1 on Treg cells and their impact on CD8+ T cell function in prostatic tumor microenvironment using transgenic adenocarcinoma of the mouse prostate (TRAMP) cells (TRAMP C1, C2 and C3) as a model system. To execute the above aim, tumor induction studies were performed. Briefly, the C57BL/6 mice were administered with serial log concentrations of TRAMP (C1-3) cells. Interestingly, the TRAMP-C3 cells do not form tumor, however, TRAMP-C1 and TRAMP-C2 cells do form tumor. After tumor development, mice were sacrificed by cervical dislocation; tumor, lung, spleen, and draining lymph nodes were harvested when the tumor size reached approximately 20mm. Single cell suspensions were prepared from different organs, cells were then stained with specific antibodies, and flow analyzed for the expression of different immune markers. Our preliminary findings demonstrated that PD-1 expression on Foxp3+ Treg cells displayed greater suppressive capacity against CD8+ T cell function in tumor, lung, spleen, and draining lymph node when compared to the control. More importantly, Foxp3+ Treg(high) PD-1(high) interaction with PDL-1 induced immunosuppression by blocking CD8+ T cells function in prostatic tumor microenvironment. In conclusion, Foxp3+ Treg(high), PD-1(high), and CD8+(low) T cells may enhance tumor progression; thus, targeting the PD-1 on Treg cells may be a possible therapy to treat prostate cancer.