Regulatory T cells act as the most important tolerance inducer for the growth and metastasis of cancer. It remains a wonder how Tregs induce tolerance for the development of cancer. Previously we have shown with melanoma patients that, increase in pTreg cell number in blood are related to the poor prognosis of the disease. pTreg and iTreg are remarkably similar and significantly different in functionality from tTreg. Here, we worked with four melanoma patients two HLA A2 + and two HLA A2 negative. PBL and tumor cells were obtained from the patients with informed consent. Treg cells were generated in four different culture conditions: isolated from tumor +PBL IVC or peptides, Mart-1 A2 or Flu A2 pulsed DC + PBL IVC, with purified CD4 cells stimulated with anti CD3 and antiCD28 plus IL-2 with or without TGF-b. Here we show some phenotypic and functional characteristics of the induced Treg cells in cultures from the patients' PBL derived CD4+CD5- cells and analyzed those in separate CTL generation assays. We observed that induced Treg cells under different conditions do not uniformly express CD25, FoxP3, PDL-1 or CTLA 4 as the known surface markers. When analyzed for their functionality, with adjusted number of cells, in suppressing the anti tumor CTL response, a significant difference was observed. The most effective Tregs cells were found to be those isolated from autologous tumor +PBL IVC or from Mart-1 peptide pulsed IVC. Those cells completely blocked the CTL induction and secreted huge amount of IL-10 upon re-stimulation. Further analysis with these different types of induced Treg cells in terms of various gene expressions will be useful to find a target molecule to block such expansion of pTregs cells for better therapeutic outcome.
Citation Format: Upendra P. Hegde, Nitya G. Chakraborty. Peripherally induced Tregs or pTregs are the potent tolerance inducer for the growth and metastasis of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3127.