微生物群特异性滤泡辅助性 T 细胞驱动三级淋巴结构及抗结直肠癌的抗肿瘤免疫

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 Bcl6 fl/fl Cd4 Cre 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.