A microbial key to unlock immunotherapy resistance: Clostridium butyricum
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Chen Y., Xu L., Jia X., et al. (2026). A microbial key to unlock immunotherapy resistance: Clostridium butyricum. The Innovation Medicine 4:100177. https://doi.org/10.59717/j.xinn-med.2026.100177
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Chen Y., Xu L., Jia X., et al. (2026). A microbial key to unlock immunotherapy resistance: Clostridium butyricum. The Innovation Medicine 4:100177. https://doi.org/10.59717/j.xinn-med.2026.100177
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Figure 1.
From bed to bench to bed: mechanism of Clostridium butyricum in suppressing colorectal cancer via direct binding and immune activation C.butyricum is significantly reduced in CRC patients compared to healthy individuals. And a clinical study in patients with advanced renal cell carcinoma showed that combining CBM588 (which contains C. butyricum) with immunotherapy significantly improved progression-free survival rates. The bacterial surface protein SecD binds specifically to GRP78 overexpressed on CRC cells. This binding inhibits the PI3K-AKT-NF-κB oncogenic signaling pathway, resulting in decreased secretion of IL-6, an immunosuppressive cytokine. Reduced IL-6 levels alleviate suppression of cytotoxic T lymphocytes (CTLs), leading to reactivation of the LCK-ZAP-70 signaling axis and enhanced production of effector cytokines IFNγ and TNFα. Meanwhile, previous studies have shown that C. butyricum fights colorectal cancer through apoptosis, cell cycle arrest, and the suppression of pro-tumorigenic inflammation. From a translational perspective, the findings of this study suggest that GRP78 represents a novel therapeutic target. Additionally, the bacterial surface protein SecD and SecD-expressing engineered bacteria also demonstrate therapeutic potential. Furthermore, butyrate produced by C. butyricum has been shown to suppress colorectal tumor. All these diverse clinical translation strategies hold the potential to convert cold tumors into hot ones.
