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Dietary commensal wrestles iron from tumor microenvironment to activate antitumoral macrophages.

Cancer Research 2024 June 5
The microbiome dictates the response to cancer immunotherapy efficacy. However, the mechanisms of how the microbiota impacts on therapy efficacy remains still poorly understood. In a recent issue of Nature Immunology, Sharma and colleagues elucidate a multifaceted, macrophage-driven mechanism exerted by a specific strain of fermented food commensal Lactiplantibacillus plantarum, LpIMB19. LpIMB19 activates tumor macrophages, resulting in the enhancement of cytotoxic CD8 T cells. LpIMB19 administration led to an expansion of tumor-infiltrating CD8 T cells and improved the efficacy of anti-PD-L1 therapy. Rhamnose-rich heteropolysaccharide (RHP), a strain-specific cell wall component, was identified as the primary effector molecule of LplMB19. TLR2 signaling and the ability of macrophages to sequester iron were both critical for RHP-mediated macrophage activation upstream of the CD8 T cell effector response and contributed to tumor cell apoptosis through iron deprivation of tumor cells. These findings reveal a well-defined mechanism connecting diet and health outcomes, suggesting that diet-derived commensals may warrant further investigation. Additionally, this work emphasizes the importance of strain-specific differences in studying microbiome-cancer interactions and the concept of "nutritional immunity" to enhance microbe-triggered antitumor immunity.

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