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Commensal bacteria stimulate antitumor responses via T cell cross-reactivity
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Commensal bacteria stimulate antitumor responses via T cell cross-reactivity
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Journal Article
Commensal bacteria stimulate antitumor responses via T cell cross-reactivity
2020
Overview
Recent studies show gut microbiota modulate antitumor immune responses; one proposed mechanism is cross-reactivity between antigens expressed in commensal bacteria and neoepitopes. We found that T cells targeting an epitope called SVYRYYGL (SVY), expressed in the commensal bacterium Bifidobacterium breve ( B . breve ), cross-react with a model neoantigen, SIYRYYGL (SIY). Mice lacking B . breve had decreased SVY-reactive T cells compared with B . breve –colonized mice, and the T cell response was transferable by SVY immunization or by cohousing mice without Bifidobacterium with ones colonized with Bifidobacterium . Tumors expressing the model SIY neoantigen also grew faster in mice lacking B . breve compared with Bifidobacterium -colonized animals. B . breve colonization also shaped the SVY-reactive TCR repertoire. Finally, SVY-specific T cells recognized SIY-expressing melanomas in vivo and led to decreased tumor growth and extended survival. Our work demonstrates that commensal bacteria can stimulate antitumor immune responses via cross-reactivity and how bacterial antigens affect the T cell landscape.
Publisher
American Society for Clinical Investigation
