Abstract 5376: Immunosuppressive T regs and MDSCs in human melanoma

Despite the ability to elicit active immune responses, most immunotherapies fail to eliminate tumors in human cancer patients. One reason immunotherapy has not met expectations may be due to immunosuppression in the local environment of the tumor. We have previously reported that untreated advanced-stage melanoma patients have increased numbers of peripheral T regs. In addition, exposure to melanoma cells in vitro expands T regs from normal human peripheral blood mononuclear cells (PBMCs). We have shown that melanoma-conditioned media have increased levels of TGF-beta, which may be responsible for the expansion of these suppressive cells in culture. Here we show that the number of peripheral T regs directly correlates with the amount of TGF-beta in the plasma of late-stage melanoma patients. We also show that melanoma patients have increased numbers of other suppressive cells, known as myeloid-derived suppressor cells (MDSCs). These MDSCs may further contribute to immunosuppression in advanced-stage melanoma patients. Finally, we show that the tumor-induced T regs and the T regs and MDSCs from the peripheral blood of melanoma patients suppress T cell responses in vitro, including proliferation, cytokine production, and cytotoxic activity. We are currently investigating whether MDSCs from melanoma patients contribute to the accumulation of T regs and whether immunotherapies used in the treatment of advanced-stage melanoma patients, particularly IL-2 and ipilimumab, affect their frequency or function. An understanding of the potential interaction between melanoma, MDSCs, and regulatory T cells will further our goal in identifying ways of blocking the function of these suppressive cells in melanoma patients to improve the effectiveness of future therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5376. doi:1538-7445.AM2012-5376