한빛사논문
- 조회225
Brandilyn A. Peters1, Melissa Wilson2,3,4, Una Moran3,5, Anna Pavlick2,3, Allison Izsak5, Todd Wechter5, Jeffrey S. Weber2,3, Iman Osman2,3,5 and Jiyoung Ahn1,3,*
1Department of Population Health, NYU School of Medicine, New York, NY 10016, USA. 2Department of Medicine, NYU School of Medicine, New York, NY, USA. 3NYU Perlmutter Cancer Center, New York, NY, USA. 4Present Address: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. 5The Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, NY, USA
*Correspondence to Jiyoung Ahn.
Abstract
Background
Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.
Methods
In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.
Results
Higher microbial community richness was associated with longer PFS in 16S and shotgun data (p < 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance of Bacteroides ovatus, Bacteroides dorei, Bacteroides massiliensis, Ruminococcus gnavus, and Blautia producta were related to shorter PFS, and Faecalibacterium prausnitzii, Coprococcus eutactus, Prevotella stercorea, Streptococcus sanguinis, Streptococcus anginosus, and Lachnospiraceae bacterium 3 1 46FAA to longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways of L-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis.
Conclusions
This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes.
논문정보
- Research article
- 2019년 10월 (BRIC 등록일 2021-10-29)
- 국외 연구진
- 의약학 > 종양의학
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