Science:粪菌移植可帮助黑色素瘤患者应答抗PD-1治疗
创作:mildbreeze 审核:mildbreeze 03月01日
  • 15名PD-1难治性黑色素瘤患者,接受源自应答者的单次FMT联合抗PD-1治疗,有6名临床获益(3名缓解、3名病情稳定),安全性良好;
  • 联合治疗引起受体菌群快速、持久的扰动,应答者的菌群变得更趋近于供体,长双歧杆菌、普氏粪杆菌等与治疗应答相关的细菌类群增多;
  • 应答者中,免疫抑制性的IL-8+ 髓系细胞减少、肿瘤内CD8+ T细胞活化增多,血液细胞因子/趋化因子/代谢组明显改变;
  • 跨界网络分析表明菌群在多组学变化中有核心作用。
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mildbreeze
几周前,Science上线了来自以色列团队的初步临床试验结果,表明粪菌移植(FMT)可促进抗PD-1治疗无效的转移性黑素瘤患者的治疗应答(查看文章)。今天Science最新发表了来自美国的一项类似的临床研究,表明源自应答者的单次FMT联合抗PD-1药物治疗,可使部分PD-1难治性黑色素瘤患者临床获益。进一步分析显示,联合治疗改变了应答受体的肠道菌群,以及外周和肿瘤内的免疫反应,可能是克服患者对于抗PD-1疗法的耐药性的关键。本期Science特别配发了对于这两项研究的评论文章(见“延伸阅读”),推荐感兴趣的读者搭配阅读。
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延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
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Science [IF:41.845]

Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients

粪菌移植克服黑色素瘤患者对于抗PD-1治疗的耐药性

10.1126/science.abf3363

02-05, Article

Abstract & Authors:展开

Abstract:收起
Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma.

First Authors:
Diwakar Davar,Amiran K Dzutsev

Correspondence Authors:
Giorgio Trinchieri,Hassane M Zarour

All Authors:
Diwakar Davar,Amiran K Dzutsev,John A McCulloch,Richard R Rodrigues,Joe-Marc Chauvin,Robert M Morrison,Richelle N Deblasio,Carmine Menna,Quanquan Ding,Ornella Pagliano,Bochra Zidi,Shuowen Zhang,Jonathan H Badger,Marie Vetizou,Alicia M Cole,Miriam R Fernandes,Stephanie Prescott,Raquel G F Costa,Ascharya K Balaji,Andrey Morgun,Ivan Vujkovic-Cvijin,Hong Wang,Amir A Borhani,Marc B Schwartz,Howard M Dubner,Scarlett J Ernst,Amy Rose,Yana G Najjar,Yasmine Belkaid,John M Kirkwood,Giorgio Trinchieri,Hassane M Zarour

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Science期刊

Modulating gut microbiota to treat cancer

2021-02-05

点评:Science配发的评论文章。

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