Myeloid-derived suppressor cells (MDSCs) and Regulatory T cells (Tregs) are the major components of immunosuppressive network that play a critical role in tumor immune evasion. The mechanisms by which tumors induce expansion of suppressive cells and the crosstalk between Gr1-MDSCs (Gr1+, CD11b+, F4/80+) and Tregs relative to TGF-β secretion remain incompletely defined. Prior studies have suggested that MDSCs may contribute to Treg recruitment in cancer. Herein, the goal of this investigation is to examine the role of TGF-β mediated generation of Tregs and Gr1-MDSCs during prostate cancer progression and clearance. To achieve this goal, matrigel system was used along with transgenic adenocarcinoma of mouse prostate (TRAMP-C1, C2 and C3 cell) in C57BL/6 mice. Interestingly, TRAMP-C3 cells are characterized as non-tumorigenic; however, TRAMP-C1 and TRAMP-C2 cells do form tumor. Mice were administered with serial log concentration of TRAMP (C1, C2 and C3) cells along with the matrigel. After three weeks, matrigels along with or without tumor were excised from tumor bearing mice, single cell suspensions was prepared and cells were flow analyzed for GR1-MDSCs and Tregs. Additionally, the TGF-β level was also estimated (colorimetric) in culture supernatant in context to MDSCs and Treg expansion. Our initial findings suggest that the expression of Gr1-MDSCs (Gr1+, CD11b+, F4/80+) and Foxp3+ Tregs increased in TRAMP-C1 and C2 as compared to TRAMP-C3 bearing C57BL/6 mice. These findings indicate that the modulation of Gr1-MDSCs and Tregs could help in tumor suppression.
Citation Format: Sanjay Kumar, James Stokes, Udai Singh, Karyn Scissum Gunn, Upender Manne, Selvarangan Ponnazhagan, Manoj K. Mishra. Gr1-MDSCs and Tregs modulate the prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2955. doi:10.1158/1538-7445.AM2017-2955