Tumor-resident probiotic Clostridium butyricum facilitates immunotherapy in colorectal cancer through secD/GRP78/IL-6 axis (PRJCA040052)

Most colorectal cancer (CRC) patients do not respond to immune checkpoint blockade (ICB) therapy. Here, we identified Clostridium butyricum as a probiotic that boosts anti-PD-1 efficacy in CRC. In orthotopic allografts of microsatellite instability-high (MSI-H) and microsatellite stable (MSS) CRC, C. butyricum potentiated tumor suppressive effect of anti-PD-1, which was verified in AOM/DSS-induced CRC and germ-free mice. Single-cell RNA-seq revealed that C. butyricum activated cytotoxic CD8+ T lymphocytes (CTLs) and impaired tumor-associated macrophages (TAMs), especially in conjunction with anti-PD-1.