Tissue-resident Lachnospiraceae family bacteria protect against colorectal carcinogenesis by promoting tumor immune surveillance

Abstract

The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8⁺ T cells in immunocompetent mice. Mechanistically, intratissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8⁺ T cell activity and maintained the immune surveillance function of CD8⁺ T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8⁺ T cells and control colorectal cancer progression.

Keywords: CD8(+) T cells; Lachnospiraceae family bacteria; colorectal cancer; degradation of lyso-glycerophospholipids; immune surveillance; tissue-resident commensal bacteria.