Abstract B6: Myeloid-derived suppressor cells from melanoma patients suppress T cell proliferation and are associated with a shorter disease-free interval.

Abstract

Abstract Immune therapies such as vaccines, immune stimulators (IL-2), and immune checkpoint regulators (anti-CTLA-4) for melanoma elicit an initial robust immunologic response to the tumor in some patients, however, the majority ultimately go on to die of their disease. This suggests that tumor eventually develop escape mechanisms meant to evade or defeat the intrinsic immune response. Myeloid-derived suppressor cells (MDSCs) have been reported in melanoma and other cancer patients and may contribute to immune suppression or counter-regulatory responses. The aim of this project was to assess the potential role of circulating MDSCs in mediating immune suppression in advanced stage melanoma patients. Methods: MDSC populations (DC14+ Lin-HLA-DR- , Lin-HLA-DR- CD11b+ CD33+) were isolated from patients with (stage I n=20, stage IV n=35)or without (n=15) melanoma. Isolated MDSC's were mixed with allogeneic CFSE-labeled T cells for a 4 day mixed lymphocyte reaction (MLR). T cell activation and proliferation were quantified. Results: Stage IV melanoma patients have increased expression (2-3 times) of some MDSC populations (Lin-HLA-DR- CD11b+ CD33+) in the circulation compared to normal and stage I melanoma patients. By MLR, these MDSC's significantly suppressed T cell proliferation (40-50% reduction) and markers of activation (20%) to a greater extent than the same population of MDSC's for normal controls. Inhibiting nitric oxide failed to restore T-cell proliferation. A shorter disease free interval is associated with increased expression of CD33+ MDSC in the circulation. Conclusion: MDSC populations are increased in the peripheral circulation of stage IV melanoma patients and these cells actively suppress T cell proliferation. Efforts are underway to better understand the melanoma related factors responsible for the induction of MDSC's and the mechanism by which these cells suppress T-cell proliferation. Citation Format: Martin D. McCarter, Kimberly Jordan. Myeloid-derived suppressor cells from melanoma patients suppress T cell proliferation and are associated with a shorter disease-free interval. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B6.