Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1
接受PD-1单抗治疗的黑色素瘤患者的临床应答及免疫相关不良事件的肠道菌群特征
10.1038/s41591-022-01698-2
02-28, Article
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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
