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利用肿瘤内微生物群:免疫微环境与免疫治疗的新视野

Harnessing intratumoral microbiota: new horizons in immune microenvironment and immunotherapy.

作者信息

Zhang Jinhe, You Zinan, Li Xinqiao, Hu Jinpeng, Li Jiamu, Jing Zhitao

机构信息

Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, People's Republic of China.

Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, 110042, People's Republic of China.

出版信息

J Transl Med. 2025 Aug 12;23(1):897. doi: 10.1186/s12967-025-06916-2.

DOI:10.1186/s12967-025-06916-2
PMID:40797326
Abstract

Microorganisms are ubiquitous in the human body, including within tumor tissues. Recent studies have demonstrated that intratumoral microbiota serve as critical regulators of the tumor microenvironment (TME), promoting the progression of solid tumors (e.g., gastric, lung, and breast cancers). These microbes modulate immune factors (such as IFN-γ and TNF-α), thereby influencing the activation and infiltration of immune cells, including T cells and macrophage. Additionally, by reshaping the immune landscape, intratumoral microbiota can dysregulate immune checkpoint expression, ultimately affecting the efficacy of cancer immunotherapy. This review synthesizes the current understanding of the origins of intratumoral microbiota, their heterogeneity across cancer types, and their intricate roles in modulating immune responses and tumor metastasis. We further discuss innovative therapeutic strategies leveraging the intratumoral microbiota, including engineered bacteria, oncolytic viruses, and nanoparticles, and address existing challenges and potential future research directions. A deeper understanding of these microbial‒host interactions may open new avenues for precise microbiota-based cancer diagnostics and personalized immunotherapeutic strategies.

摘要

微生物在人体中无处不在,包括肿瘤组织内。最近的研究表明,肿瘤内微生物群是肿瘤微环境(TME)的关键调节因子,促进实体瘤(如胃癌、肺癌和乳腺癌)的进展。这些微生物调节免疫因子(如IFN-γ和TNF-α),从而影响免疫细胞(包括T细胞和巨噬细胞)的激活和浸润。此外,通过重塑免疫格局,肿瘤内微生物群可使免疫检查点表达失调,最终影响癌症免疫治疗的疗效。本综述综合了目前对肿瘤内微生物群起源、其在不同癌症类型中的异质性及其在调节免疫反应和肿瘤转移中的复杂作用的理解。我们进一步讨论了利用肿瘤内微生物群的创新治疗策略,包括工程菌、溶瘤病毒和纳米颗粒,并探讨了现有挑战和未来潜在的研究方向。对这些微生物-宿主相互作用的更深入理解可能为基于微生物群的精确癌症诊断和个性化免疫治疗策略开辟新途径。

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Harnessing intratumoral microbiota: new horizons in immune microenvironment and immunotherapy.利用肿瘤内微生物群:免疫微环境与免疫治疗的新视野
J Transl Med. 2025 Aug 12;23(1):897. doi: 10.1186/s12967-025-06916-2.
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本文引用的文献

1
promotes metastasis of breast cancer via the miR-21-3p/FOXO3 axis.通过miR-21-3p/FOXO3轴促进乳腺癌转移。
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Preclinical and clinical evaluation of intratumoral injection of an IL-12 expressing SKV-012 oncolytic virus for advanced solid tumors.瘤内注射表达白细胞介素-12的SKV-012溶瘤病毒用于晚期实体瘤的临床前和临床评估。
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Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance.
肿瘤内微生物群的空间异质性:癌症免疫治疗耐药性的新前沿。
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Integrated spatial multi-omics profiling of Fusobacterium nucleatum in breast cancer unveils its role in tumour microenvironment modulation and cancer progression.乳腺癌中具核梭杆菌的综合空间多组学分析揭示了其在肿瘤微环境调节和癌症进展中的作用。
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Intratumoral microbiome: implications for immune modulation and innovative therapeutic strategies in cancer.肿瘤内微生物群:对癌症免疫调节和创新治疗策略的影响
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Tumor-colonizing Lachnoclostridium-mediated chemokine expression enhances the immune infiltration of bladder urothelial carcinoma.肿瘤定植的迟缓梭菌介导的趋化因子表达增强膀胱尿路上皮癌的免疫浸润。
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Bisphenol S impairs oocyte quality by inducing gut microbiota dysbiosis.双酚S通过诱导肠道微生物群失调损害卵母细胞质量。
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Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma.多组学分析揭示了肿瘤内细菌与神经胶质瘤之间的相互作用。
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Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy.肿瘤内微生物群对肿瘤发生、抗肿瘤免疫及基于微生物的癌症治疗的影响。
Front Oncol. 2024 Sep 26;14:1429722. doi: 10.3389/fonc.2024.1429722. eCollection 2024.
10
Leucine restriction ameliorates Fusobacterium nucleatum-driven malignant progression and radioresistance in nasopharyngeal carcinoma.亮氨酸限制可改善具核梭杆菌驱动的鼻咽癌恶性进展和放射抵抗。
Cell Rep Med. 2024 Oct 15;5(10):101753. doi: 10.1016/j.xcrm.2024.101753. Epub 2024 Oct 1.