Ongoing priming of naïve melanoma/melanocyte specific CD8 T cells occurs in hosts with vitiligo (P225) (162.6)

Abstract

Abstract Vitiligo, the autoimmune destruction of melanocytes, correlates with improved survival in melanoma patients although it is often disregarded as a side effect of robust anti-tumor T cell responses. We have shown that antigen provided by vitiligo is required for long-lived CD8 T cell memory against melanoma-expressed self-antigens. However, the possibility that autoimmune melanocyte destruction itself may prime CD8 T cells able to cross-react against melanoma has not been investigated. Previously, we reported vitiligo development in 60% of mice depleted of regulatory CD4 T cells while bearing established B16 melanoma tumors. To probe the immunogenicity of vitiligo, we transferred naïve melanocyte-antigen specific pmel CD8 T cells in to actively depigmenting hosts. We find that CD8 T cell activation and proliferation occurs in an antigen-specific manner only in hosts with vitiligo. Furthermore, although the pmel cells do not produce IFN-γ, the cells produce Granzyme B and express LAMP-1 and P selectin ligand. Interestingly, although vitiligo-primed CD8 T cells appear strongly activated, the cells do not form robust memory populations in the presence of CD4 T regulatory cells. Ongoing studies aim to investigate the anti-melanoma capabilities of vitiligo-primed CD8 T cells. These studies will further enhance our understanding of the direct relationship between tumor immunity and autoimmunity, and the contributions of these cells in protecting against recurrent tumor growth.