Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice
Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice
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DOI：
10.1038/s41564-020-00831-6
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发表时间：
2021-01-11
影响因子：
28.3
通讯作者：
Park, Hansoo
中科院分区：
文献类型：
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作者：
Lee, Se-Hoon;Cho, Sung-Yup;Park, Hansoo
肠道微生物组可以影响肿瘤的发展和癌症治疗的疗效（1-5）;然而，抗肿瘤细菌菌株的多组学特征尚未完全阐明。在这项研究中，我们整合了细菌的宏基因组学，基因组学和转录组学，以及对小鼠肠道转录组和血清代谢组数据的分析，以揭示细菌决定癌症治疗效果的另一种机制。在对96例非小细胞肺癌患者的肠道微生物组分析中，两歧双歧杆菌在对治疗有反应的患者中含量丰富。然而，当我们用商业化的B.两歧，以建立潜在的治疗用途的相关性，只有特定的B。两歧菌株通过引发抗肿瘤宿主免疫应答与PD-1阻断或奥沙利铂治疗协同降低肿瘤负荷。在小鼠中，这些菌株通过增强干扰素-γ的产生来诱导免疫背景的调整，这可能是通过增强免疫刺激分子和代谢物的生物合成。
The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics(1-5); however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-gamma, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.