Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Cell Rep. 2020 Feb 11;30(6):1753-1766.e6. doi: 10.1016/j.celrep.2020.01.035.
Growing evidence supports the importance of gut microbiota in the control of tumor growth and response to therapy. Here, we select prebiotics that can enrich bacterial taxa that promote anti-tumor immunity. Addition of the prebiotics inulin or mucin to the diet of C57BL/6 mice induces anti-tumor immune responses and inhibition of BRAF mutant melanoma growth in a subcutaneously implanted syngeneic mouse model. Mucin fails to inhibit tumor growth in germ-free mice, indicating that the gut microbiota is required for the activation of the anti-tumor immune response. Inulin and mucin drive distinct changes in the microbiota, as inulin, but not mucin, limits tumor growth in syngeneic mouse models of colon cancer and NRAS mutant melanoma and enhances the efficacy of a MEK inhibitor against melanoma while delaying the emergence of drug resistance. We highlight the importance of gut microbiota in anti-tumor immunity and the potential therapeutic role for prebiotics in this process.
越来越多的证据支持肠道微生物群在控制肿瘤生长和对治疗的反应中的重要性。在这里,我们选择能够富集促进抗肿瘤免疫的细菌类群的益生元。在 C57BL/6 小鼠的饮食中添加益生元菊粉或粘蛋白会诱导抗肿瘤免疫反应,并抑制皮下植入同基因小鼠模型中 BRAF 突变型黑色素瘤的生长。粘蛋白不能抑制无菌小鼠的肿瘤生长,表明肠道微生物群是激活抗肿瘤免疫反应所必需的。菊粉和粘蛋白驱动微生物群的不同变化,因为菊粉而不是粘蛋白限制了结肠癌和 NRAS 突变型黑色素瘤的同基因小鼠模型中的肿瘤生长,并增强了 MEK 抑制剂对黑色素瘤的疗效,同时延迟了耐药性的出现。我们强调了肠道微生物群在抗肿瘤免疫中的重要性,以及益生元在这一过程中的潜在治疗作用。