期刊
IMMUNITY
卷 54, 期 12, 页码 2812-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2021.11.003
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资金
- UPMC Children's Hospital of Pittsburgh/R.K. Mellon Institute for Pediatric Research
- NIH [R21 CA249074, T32 5T32CA082084-18, T32AI089443, R01 CA203689, P01 AI108545]
- Damon Runyon Cancer Research Foundation (DRCRF postdoctoral fellowship)
- Eden Hall Foundation
- Hillman Cancer Cen-ter (Hillman Postdoctoral Fellowship for Innovative Cancer Research)
The study showed that introducing specific intestinal bacteria can enhance anti-colorectal cancer immunity and promote tumor control. This anti-tumor immunity is dependent on CD4(+) T cells, B cells, and NK cells.
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.
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