The microbiome dictates the response to cancer immunotherapy efficacy. However, the mechanisms of how the microbiota impacts therapy efficacy remain 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 plantarum strain IMB19, LpIMB19. LpIMB19 activates tumor macrophages, resulting in the enhancement of cytotoxic cluster differentiation 8 (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, a strain-specific cell wall component, was identified as the primary effector molecule of LplMB19. Toll-like receptor 2 signaling and the ability of macrophages to sequester iron were both critical for rhamnose-rich heteropolysaccharide-mediated macrophage activation upstream of the CD8 T-cell effector response and contributed to tumor cell apoptosis through iron deprivation. 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.

中文翻译：

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饮食共生从肿瘤微环境中夺取铁以激活抗肿瘤巨噬细胞。


微生物组决定了对癌症免疫治疗疗效的反应。然而，微生物群如何影响治疗效果的机制仍然知之甚少。在最近一期的《自然免疫学》杂志上，Sharma 及其同事阐明了发酵食品植物共生菌株 IMB19 的特定菌株 IMB19 LpIMB19 施加的多方面、巨噬细胞驱动的机制。LpIMB19 激活肿瘤巨噬细胞，导致细胞毒性簇分化 8 （CD8） T 细胞增强。LpIMB19 给药导致肿瘤浸润 CD8 T 细胞扩增，提高抗 PD-L1 治疗的疗效。富含鼠李糖的异多糖是一种菌株特异性细胞壁成分，被确定为 LplMB19 的主要效应分子。Toll 样受体 2 信号传导和巨噬细胞隔离铁的能力对于富含鼠李糖的异多糖介导的巨噬细胞活化都至关重要CD8 T 细胞效应反应的上游，并通过铁剥夺导致肿瘤细胞凋亡。这些发现揭示了将饮食与健康结果联系起来的明确机制，表明饮食衍生的共生体可能需要进一步研究。此外，这项工作强调了菌株特异性差异在研究微生物组-癌症相互作用和“营养免疫”概念以增强微生物触发的抗肿瘤免疫方面的重要性。