ASPO Abstracts
Gut microbiome differences between immune checkpoint inhibitor responders and non-responders in non-small cell lung cancer
Category: Molecular Epidemiology & Environment
Conference Year: 2019
Abstract Body:
Purpose: The microbiome has been recognized as a modifier of tumor initiation, progression, and therapeutics. This prospective study aims to understand the role of the microbiome in patients with non-small cell lung cancer (NSCLC) undergoing treatment with immune checkpoint inhibitor (ICI) therapy, and examine whether gut microbiota are associated with clinical response. Methods: We examined baseline and follow-up stool samples of stage III/IV NSCLC patients (n=26) undergoing ICI (anti-PD-1, PD-L1, CTLA-4). Stool specimens were collected at home within 72hr of the initial ICI dose (baseline) and after the 4th ICI dose (follow-up), preserved in RNAlater, and extracted using the Qiagen PowerLyzer PowerSoil DNA isolation kit. The V1-V3 region of the 16S rRNA gene was sequenced on Illumina MiSeq, and raw data were processed using QIIME2. Principal coordinates analyses and linear discriminant analysis effect size were used to identify differences in gut microbial profiles between clinical responders (cR) and non-responders (cNR). For this analysis, cR (n=15) experienced complete/partial response to ICI and cNR (n=11) experienced stable/progressive disease as determined by CT scan within 6 months of treatment start.Results: Baseline gut bacterial community structures differed significantly between cR and cNR (PERMANOVA p=0.03). cR were significantly more likely than cNR to have greater abundance of Ruminococcus, Clostridiales, Christensenellaceae, Dehalobacterium, Synergistes, Alphaproteobacteria, and Lactococcus, and less likely to have Epsilonproteobacteria, Sutterella, Campylobacter, Fusobacteria, and Collinsella prior to ICI therapy. Microbial alpha diversity (within sample variation; Chao1) at baseline appeared higher among cR vs. cNR (not statistically significant). Gut microbial composition did not appear to change throughout the course of ICI treatment (PERMANOVA p=0.85).Conclusions: These results demonstrate an association between gut microbiota composition and clinical responsiveness to ICI. Our study identified additional bacterial taxa contributing to ICI clinical response in NSCLC. Future studies incorporating microbial metatranscriptomics will allow for additional insight into the functional role of gut microbiota in clinical response to ICI therapy.
Keywords: Microbiome, lung cancer, immunotherapy