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Overacre-Delgoffe, Abigail E.; Bumgarner, Hannah J.; Cillo, Anthony R.; Burr, Ansen H.P.; Tometich, Justin T.; Bhattacharjee, Amrita; Bruno, Tullia C.; Vignali, Dario A.A.; Hand, Timothy W.
Immunity, 12/2021, Letnik: 54, Številka: 12Journal Article
The composition of the intestinal microbiota is associated with both the development of tumors and the efficacy of anti-tumor immunity. Here, we examined the impact of microbiota-specific T cells in anti-colorectal cancer (CRC) immunity. Introduction of Helicobacter hepaticus (Hhep) in a mouse model of CRC did not alter the microbial landscape but increased tumor infiltration by cytotoxic lymphocytes and inhibited tumor growth. Anti-tumor immunity was independent of CD8+ T cells but dependent upon CD4+ T cells, B cells, and natural killer (NK) cells. Hhep colonization induced Hhep-specific T follicular helper (Tfh) cells, increased the number of colon Tfh cells, and supported the maturation of Hhep+ tumor-adjacent tertiary lymphoid structures. Tfh cells were necessary for Hhep-mediated tumor control and immune infiltration, and adoptive transfer of Hhep-specific CD4+ T cells to Tfh cell-deficient Bcl6fl/flCd4Cre mice restored anti-tumor immunity. Thus, introduction of immunogenic intestinal bacteria can promote Tfh-associated anti-tumor immunity in the colon, suggesting therapeutic approaches for the treatment of CRC. Display omitted •Helicobacter hepaticus (Hhep) colonization reduces colorectal cancer burden in mice•Hhep induces CD4+ Tfh cell- and B cell-dependent anti-colorectal cancer immunity•Hhep colonization expands peritumoral tertiary lymphoid structures (TLSs)•Hhep-specific Tfh cells promote both TLSs and anti-tumor immunity The effectiveness of immune-mediated cancer therapy is modulated by the microbiota. Overacre-Delgoffe et al. reveal that colonization of colon tumor-bearing mice with an immunogenic intestinal bacteria, Helicobacter hepaticus, induces Hhep-specific T follicular helper cells and tumor-adjacent lymphoid structures, thereby promoting anti-tumor immunity.
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in: SICRIS
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