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脑肿瘤诱导的肠道微生物群失调会调节免疫治疗的疗效。

Gut microbiota dysbiosis induced by brain tumors modulates the efficacy of immunotherapy.

作者信息

Kim Hyeon Cheol, Kim Hyun-Jin, La Jeongwoo, Park Won Hyung, Park Sang Hee, Kang Byeong Hoon, Kim Yumin, Lee Heung Kyu

机构信息

Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Life Science Institute, KAIST, Daejeon 34141, Republic of Korea.

Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.

出版信息

Cell Rep. 2025 Jul 22;44(7):115825. doi: 10.1016/j.celrep.2025.115825. Epub 2025 Jun 26.

Abstract

Although the influence of gut microbiota on various tumors has gained recognition, the intricate mechanisms underlying its effects on brain tumors remain largely unexplored. Our study aims to discover crucial gut microbiota that significantly bolster the immune response against brain tumors. Employing a murine model, we utilize 16S rRNA sequencing to analyze the evolution of gut microbiota alongside tumor progression, and we intervene with dietary adjustments using tryptophan to restore microbiota alterations. Tryptophan supplementation not only reverses these microbial changes but also significantly enhances survival by boosting T cell circulation and improves the efficacy of immunotherapy. Among the microbial species that respond positively to tryptophan, Duncaniella dubosii emerges as a pivotal contributor, replicating tryptophan's immunomodulatory effects. This study underscores the potential of targeting gut microbiota to enhance immunotherapy efficacy, particularly through mechanisms involving T cell modulation.

摘要

尽管肠道微生物群对各种肿瘤的影响已得到认可,但其对脑肿瘤影响的复杂机制仍 largely 未被探索。我们的研究旨在发现能显著增强针对脑肿瘤免疫反应的关键肠道微生物群。利用小鼠模型,我们使用 16S rRNA 测序来分析肠道微生物群随肿瘤进展的演变,并通过补充色氨酸进行饮食调整来干预微生物群的变化。补充色氨酸不仅能逆转这些微生物变化,还能通过促进 T 细胞循环显著提高生存率,并提高免疫治疗的疗效。在对色氨酸有积极反应的微生物物种中,杜氏邓肯菌成为关键贡献者,复制了色氨酸的免疫调节作用。这项研究强调了靶向肠道微生物群以提高免疫治疗疗效的潜力,特别是通过涉及 T 细胞调节的机制。

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