Science子刊:揭示肠道菌群促进肠外抗肿瘤免疫的关键机制
创作:章台柳 审核:章台柳 04月01日
  • 免疫检查点阻断治疗(ICT)诱导特定的内源性肠道细菌易位至次级淋巴器官(肠系膜淋巴结(MLN)和肿瘤引流淋巴结(TDLN))和皮下黑色素瘤;
  • 大量的细菌易位激活DC,并诱导抗肿瘤效应T细胞反应,而DC也有助于肠道细菌易位至次级淋巴器官;
  • MLN调节TDLN和肿瘤内肠道细菌依赖性的抗肿瘤反应;
  • ICT诱导MLN中HEV小静脉的淋巴管生成和扩张;
  • 抗生素治疗导致肠道细菌向MLN和TDLN的转移减少,减弱DC和效应CD8+T细胞反应,减弱机体对ICT的响应。
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章台柳
肠道微生物群,特别是肠道细菌,对于免疫检查点阻断治疗(ICT)癌症的效果至关重要。然而,肠道微生物群如何增强肠外抗癌免疫反应,尚不清楚。Science Immunology近期发表的文章,发现ICT诱导特定的内源性肠道细菌易位至次级淋巴器官,激活DC并诱导抗肿瘤效应T细胞的反应,增强肠道外抗肿瘤免疫反应。研究阐明了肠道微生物群促进肠外抗癌免疫的关键机制。
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Science Immunology [IF:30.63]

Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity

免疫检查点阻断诱导肠道微生物群易位,增强肠外抗肿瘤免疫

10.1126/sciimmunol.abo2003

03-03, Article

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Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8+ T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.

First Authors:
Yongbin Choi

Correspondence Authors:
Andrew Y Koh

All Authors:
Yongbin Choi,Jake N Lichterman,Laura A Coughlin,Nicole Poulides,Wenling Li,Priscilla Del Valle,Suzette N Palmer,Shuheng Gan,Jiwoong Kim,Xiaowei Zhan,Yajing Gao,Bret M Evers,Lora V Hooper,Chandrashekhar Pasare,Andrew Y Koh

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Nature Immunology期刊

Microbiome checkpoint

2023-03-23

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