RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The gut microbiota in cancer immunity and immunotherapy.
The gut microbiota in cancer immunity and immunotherapy.
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人类胃肠道中栖息着数万亿微生物,包括细菌、真菌和病毒,共同构成肠道微生物群。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,肠道微生物群发生改变、富含致病菌时,可主动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 Lactobacillus 和 Bifidobacterium)已成为用于癌症预防的治疗性益生菌以及癌症治疗的佐剂。肠道微生物群还与免疫治疗的疗效密切相关。本综述总结了致病菌和有益共生菌对癌症中多种固有和适应性免疫细胞群的影响,包括 T 细胞、B 细胞、NK 细胞、固有淋巴细胞和髓源性抑制细胞。本综述还探讨了肠道微生物群影响免疫治疗疗效的机制,例如对固有免疫细胞和 CD8 + T 细胞的调节。鉴于其重要性,越来越多的研究已开发出靶向肠道微生物群的方法,以改善免疫治疗结局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、噬菌体疗法和粪菌移植。本综述还评估了利用肠道微生物群预测免疫治疗结局的临床应用。
总体而言,目前对肿瘤微环境中宿主‒微生物相互作用的认识,为将微生物群研究转化为临床实践奠定了关键基础,最终使患者获益。
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.
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