Microbiome-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer.
Overacre-Delgoffe, A. E.; Cillo, A. R.; Bumgarner, H. J.; Burr, A. H.; Tometich, J. T.; Bhattacharjee, A.; Bruno, T. C.; Vignali, D. A.; Hand, T.
Show abstract
Colorectal cancer (CRC) is a common and deadly disease, and patients with metastatic tumors often fail to respond to therapy. While select members of the microbiome are associated with improved anti-tumor immunity, mechanistic understanding of how the microbiome provides a benefit is lacking. We show that modification of the CRC-associated microbiome with a single immunogenic commensal bacteria can alter T cell differentiation, inhibit tumor growth, and increase survival. Microbiome-driven control of CRC required the formation of colonic tertiary lymphoid structures (TLS) and increased infiltration of the tumor with cytotoxic immune cells. In the context of CRC, CD4+ T cells specific to the newly introduced commensals differentiated into T follicular helper cells and were necessary for the formation of TLS, immune infiltration of the tumor, and control over CRC. Thus, modification of the intestinal T cell response by the microbiome can be used to augment anti-tumor immunity in colorectal cancer.
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