CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The cancer-microbiome axis: Mechanisms and emerging therapeutic strategies.
The cancer-microbiome axis: Mechanisms and emerging therapeutic strategies.
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人类微生物组已成为癌症发生、发展和治疗反应的关键调节因素。测序和功能谱分析技术的进步揭示,共生微生物——尤其是细菌——与宿主免疫和代谢通路密切相互作用,在多种癌症类型中影响肿瘤免疫。肠道微生物组失调与肿瘤发生、免疫逃逸和治疗耐药相关,而特定微生物类群和代谢物已被证明可增强抗肿瘤免疫反应。这些发现推动了基于微生物组的治疗策略的发展,旨在重塑宿主-肿瘤相互作用。本综述总结了目前对癌症-微生物组轴的理解,特别关注利用微生物调节的治疗干预措施。
我们讨论了粪菌移植(FMT)作为一种早期概念验证方法,展示了微生物组恢复免疫检查点抑制剂反应性的能力,同时也强调了其在变异性、标准化和机制不确定性方面的局限性。随后,我们探讨了新兴的还原论策略,包括补充单一细菌菌株、明确组成的菌群联合体,以及设计用于在肿瘤微环境内直接递送免疫调节有效载荷的工程化微生物。
最后,我们探讨了微生物调节如何与化疗、激素治疗和细胞免疫治疗等常规癌症疗法相互作用。总体而言,这些研究展示了一个快速发展的领域,正从相关性观察转向基于机制的治疗设计。尽管仍存在显著的技术和生物学挑战,微生物学、免疫学和合成生物学的持续整合有望将基于微生物组的干预措施转化为安全、精准和有效的癌症疗法。
The human microbiome has emerged as a critical modulator of cancer development, progression, and therapeutic response. Advances in sequencing and functional profiling have revealed that commensal microorganisms—particularly bacteria—interact closely with host immune and metabolic pathways, influencing tumor immunity across multiple cancer types.
Dysbiosis of the gut microbiome has been associated with tumorigenesis, immune evasion, and resistance to therapy, while specific microbial taxa and metabolites have been shown to enhance antitumor immune responses. These discoveries have catalyzed the development of microbiome-based therapeutic strategies aimed at reshaping host–tumor interactions. This review summarizes current understanding of the cancer–microbiome axis, with a particular focus on therapeutic interventions that leverage microbial modulation.
We discuss fecal microbiota transplantation (FMT) as an early, proof-of-concept approach demonstrating the capacity of the microbiome to restore responsiveness to immune checkpoint inhibitors, while also highlighting its limitations related to variability, standardization, and mechanistic uncertainty.
We then examine emerging reductionist strategies, including supplementation with individual bacterial strains, defined consortia, and engineered microbes designed to deliver immunomodulatory payloads directly within the tumor microenvironment.
Finally, we explore how microbial modulation interfaces with conventional cancer therapies such as chemotherapy, hormonal therapy, and cellular immunotherapies.
Together, these studies illustrate a rapidly evolving field transitioning from correlative observations to mechanistically informed therapeutic design. While significant technical and biological challenges remain, continued integration of microbiology, immunology, and synthetic biology holds promise for translating microbiome-based interventions into safe, precise, and effective cancer therapies.
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