Microbiota-specific T follicular helper cells drive tertiary lymphoid structures and anti-tumor immunity against colorectal cancer

• DOI: 10.1016/j.immuni.2021.11.003
• Publication Date: 2021-12-02T15:30:30Z
• Authors: Abigail E. Overac...; Hannah J. Bumgarner; Anthony R. Cillo; Ansen H.P. Burr; Justin T. Tometich; Amrita Bhattacharjee; Tullia C. Bruno; Dario A.A. Vignali; Timothy W. Hand
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; T Follicular Helper Cells; Colon; B-Lymphocyte Subsets; Gastrointestinal Microbiome; Helicobacter Infections; 3. Good health; Killer Cells, Natural; Disease Models, Animal; Mice; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Tertiary Lymphoid Structures; Proto-Oncogene Proteins c-bcl-6; Animals; Humans; Colorectal Neoplasms; Helicobacter hepaticus

SummaryColorectal 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.