小柯机器人

美国国立癌症研究所Amiran K. Dzutsev等研究人员合作揭示接受抗PD-1治疗的黑色素瘤患者的临床反应和免疫相关不良事件的肠道微生物群特征。该研究于2022年2月28日在线发表于国际一流学术期刊《自然—医学》。

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

Issue&Volume: 2022-02-28

Abstract: 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. Integrated analysis of microbiome and host cell transcriptional data on clinically annotated cohorts of patients with melanoma who were treated with anti-programmed cell death protein-1, uncovers new associations of streptococcus species with immune-related adverse effects and finds consistent microbiome associations with clinical outcomes.

DOI: 10.1038/s41591-022-01698-2

Source: https://www.nature.com/articles/s41591-022-01698-2

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex