Professor Michael Fischbach, Stanford University. Title: Understanding and manipulating immune modulation by the microbiome

Abstract: Certain members of the commensal microbiota elicit a potent T cell response upon colonization. In this talk, I will describe two recent projects from my research group that share the goal of characterizing and manipulating anti-commensal immunity. In the first project, we explore the functional properties of colonist-induced T cells by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, engineered S. epidermidis elicits tumor-specific T cells that circulate, infiltrate local and metastatic lesions, and exert cytotoxic activity, showing that the immune response to a colonist can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal. In the second, we colonize germ-free mice with a complex defined community (>100 bacterial strains) and profile T cell responses to each strain individually. We find that T cell recognition of Firmicutes is focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.