Immunotherapies designed to bolster endogenous immune responses against tumors, in the form of checkpoint blockade, have vastly improved survival for a host of cancers. However, despite these novel approaches, metastatic melanoma remains associated with high mortality and rapid progression, and a subset of patients do not respond robustly to checkpoint blockade. Development of new methods to boost endogenous immune responses against melanoma thus constitutes a critical step toward the management of disease. Of note, initiating immune responses against nonmutated melanocyte-specific protein antigens has shown efficacy in augmenting immunotherapies. Vitiligo is an autoimmune disease characterized by immune-mediated destruction of melanocytes, though the etiology of this disease remains poorly understood. Skin-resident microbes have been recently demonstrated to exert a profound effect on immune processes of the skin, including those that are associated with vitiligo progression. Identifying skin-resident microbes that initiate or exacerbate antimelanocyte immune responses, as well as the precise pathways that mediate these processes, may provide a novel framework for the development of immunotherapies to augment antimelanoma immune responses. Thus, we have recruited a cohort of individuals with and without vitiligo and profiled their skin microbiomes at various body sites. We have found that vitiligo subjects harbor a skin microbiota that is unique from healthy subjects, and have isolated several vitiligo-associated bacteria. Notably, a previously uncultured Corynebacterium species appears in greater abundance on vitiligo subjects than on control subjects. The immunomodulatory potential of this novel bacterium will be explored in murine models developed by our laboratory, including an adapted mouse model of vitiligo. Interrogation of this host-microbiome relationship may thus lead to the identification of novel targets and pathways by which to treat vitiligo and augment melanoma immunotherapies.
Citation Format: Ivan Vujkovic-Cvijin. Vitiligo and melanoma: The role of cutaneous human commensal bacteria in antimelanocyte immune responses [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B068.