创作:aluba 审核:aluba 04月01日
  • 纳入94名接受PD-1单抗治疗的黑色素瘤患者;
  • 治疗前(而非治疗4个月后)的肠道菌群组成与治疗一年后的临床结局相关;
  • 将新队列与已发表的4个队列的数据进行荟萃分析,放线菌门、毛螺菌科/瘤胃球菌科与较好的临床应答相关,而革兰氏阴性菌与炎症肠道基因特征、血液中性粒细胞/淋巴细胞比值升高及较差的临床应答相关;
  • 毛螺菌科富集与较好的临床应答相关,链球菌属富集与较差的临床应答相关,而两者的富集均与免疫相关不良事件相关。
Nature Medicine上发表的一项最新研究,在94名接受PD-1单抗治疗的黑色素瘤患者中发现,治疗前(而非治疗后)的肠道菌群特征与临床应答相关。综合本研究中的队列及已发表研究中的4个队列进行荟萃分析,鉴定出以放线菌门及毛螺菌科/瘤胃球菌科富集为特征的菌群与较好的临床应答相关,而与系统性及肠道炎症相关的革兰氏阴性菌的富集与较差的临床应答相关。另外,毛螺菌科及链球菌属的富集分别与较好及较差的预后相关,并与不同的免疫相关不良事件相关。尽管菌群特征与患者对PD-1单抗的应答的关联受到地理因素影响,基于多个队列的菌群数据训练的机器学习模型可预测不同队列的患者对PD-1单抗的应答。
Nature Medicine [IF:87.241]

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1



02-28, Article

Abstract & Authors:展开

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment. Meta-analysis and other bioinformatic analyses of the combined data show that bacteria associated with favorable response are confined within the Actinobacteria phylum and the Lachnospiraceae/Ruminococcaceae families of Firmicutes. Conversely, Gram-negative bacteria were associated with an inflammatory host intestinal gene signature, increased blood neutrophil-to-lymphocyte ratio, and unfavorable outcome. Two microbial signatures, enriched for Lachnospiraceae spp. and Streptococcaceae spp., were associated with favorable and unfavorable clinical response, respectively, and with distinct immune-related adverse effects. Despite between-cohort heterogeneity, optimized all-minus-one supervised learning algorithms trained on batch-corrected microbiome data consistently predicted outcomes to programmed cell death protein-1 therapy in all cohorts. Gut microbial communities (microbiotypes) with nonuniform geographical distribution were associated with favorable and unfavorable outcomes, contributing to discrepancies between cohorts. Our findings shed new light on the complex interaction between the gut microbiome and response to cancer immunotherapy, providing a roadmap for future studies.

First Authors:
John A McCulloch,Diwakar Davar,Richard R Rodrigues

Correspondence Authors:
Hassane M Zarour,Giorgio Trinchieri,Amiran K Dzutsev

All Authors:
John A McCulloch,Diwakar Davar,Richard R Rodrigues,Jonathan H Badger,Jennifer R Fang,Alicia M Cole,Ascharya K Balaji,Marie Vetizou,Stephanie M Prescott,Miriam R Fernandes,Raquel G F Costa,Wuxing Yuan,Rosalba Salcedo,Erol Bahadiroglu,Soumen Roy,Richelle N DeBlasio,Robert M Morrison,Joe-Marc Chauvin,Quanquan Ding,Bochra Zidi,Ava Lowin,Saranya Chakka,Wentao Gao,Ornella Pagliano,Scarlett J Ernst,Amy Rose,Nolan K Newman,Andrey Morgun,Hassane M Zarour,Giorgio Trinchieri,Amiran K Dzutsev

Nature Reviews Clinical Oncology期刊

Gut microbes as biomarkers of ICI response — sharpening the focus