Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Adv Exp Med Biol. 2020;1219:93-107. doi: 10.1007/978-3-030-34025-4_5.
Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe 'transkingdom network' with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.
癌症在多细胞生物中发展，源于无视合作规则并逃避抗癌监测机制的细胞。肿瘤发生是宿主和微生物群共同遇到的问题，微生物群是生活在身体外部和内部上皮表面的大量微生物。人类微生物群最大的群落存在于胃肠道中，其中共生、共生和病原微生物与肠道屏障和肠道黏膜淋巴组织相互作用，形成肿瘤微环境，使癌细胞得以生长或死亡。肠道微生物群的异常组成和功能（失调）通过诱导炎症、促进细胞生长和增殖、削弱免疫监视以及改变宿主的食物和药物代谢或其他生化功能与肿瘤发生有关。然而，最近的研究还确定了几种肠道微生物群支持宿主对抗癌症的机制。这些机制包括利用抗原模拟、化疗药物的生物转化以及其他增强抗癌免疫反应和提高癌症免疫治疗效果的机制。在这个快速发展的领域中进一步研究预计将确定具有肿瘤抑制特性的其他微生物代谢物，绘制宿主-微生物“跨界网络”与癌细胞之间复杂相互作用的图谱，并阐明特定肠道微生物群落配置对免疫检查点抑制剂治疗影响的细胞和分子途径。
