Xie Mingxu, Li Xiang, Lau Harry Cheuk-Hay, Yu Jun
Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Center for Gut Microbiome Research, Med-X Institute Centre, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Cell Mol Immunol. 2025 Aug 6. doi: 10.1038/s41423-025-01326-2.
The human gastrointestinal tract harbors trillions of microorganisms, including bacteria, fungi, and viruses, to form the gut microbiota. Cumulative evidence has demonstrated the critical impact of gut microbes on cancer immunity. In cancer, an altered gut microbiota enriched with pathogenic bacteria can actively promote immune evasion and disrupt antitumor immunity, thereby supporting tumor growth and survival. Conversely, beneficial commensal bacteria (e.g., Lactobacillus and Bifidobacterium) have emerged as therapeutic probiotics for cancer prevention and as adjuvants for cancer therapy. The gut microbiota is also closely linked to the efficacy of immunotherapy. This review summarizes the effects of pathogenic bacteria and beneficial commensals, including T cells, B cells, natural killer cells, innate lymphoid cells, and myeloid-derived suppress cells, on various innate and adaptive immune cell populations in cancer. It also explores the mechanisms by which the gut microbiota influences immunotherapy efficacy, such as the modulation of innate immune cells and CD8 T cells. Given its importance, an increasing number of studies have developed approaches to target the gut microbiota to improve immunotherapy outcomes and reduce immune-related adverse events. These strategies include antimicrobial intervention, probiotics, prebiotics/dietary modifications, microbial metabolites, phage therapy, and fecal microbiota transplantation. This review also evaluates clinical applications that use the gut microbiota to predict immunotherapy outcomes. Overall, the current understanding of host‒microbe interactions within the tumor microenvironment has laid a critical foundation for the translation of microbiota research into clinical practice, ultimately benefiting patients.
人类胃肠道中栖息着数万亿微生物,包括细菌、真菌和病毒,它们共同构成了肠道微生物群。越来越多的证据表明肠道微生物对癌症免疫具有关键影响。在癌症中,富含病原菌的肠道微生物群改变可积极促进免疫逃逸并破坏抗肿瘤免疫,从而支持肿瘤生长和存活。相反,有益共生菌(如乳酸杆菌和双歧杆菌)已成为癌症预防的治疗性益生菌和癌症治疗的佐剂。肠道微生物群还与免疫治疗的疗效密切相关。本综述总结了病原菌和有益共生菌,包括T细胞、B细胞、自然杀伤细胞、先天淋巴细胞和髓系来源的抑制细胞,对癌症中各种先天和适应性免疫细胞群体的影响。它还探讨了肠道微生物群影响免疫治疗疗效的机制,如对先天免疫细胞和CD8 T细胞的调节。鉴于其重要性,越来越多的研究开发了针对肠道微生物群的方法,以改善免疫治疗效果并减少免疫相关不良事件。这些策略包括抗菌干预、益生菌、益生元/饮食调整、微生物代谢产物、噬菌体疗法和粪便微生物群移植。本综述还评估了利用肠道微生物群预测免疫治疗结果的临床应用。总体而言,目前对肿瘤微环境中宿主与微生物相互作用的理解为将微生物群研究转化为临床实践奠定了关键基础,最终使患者受益。