371 The association of the gut microbiota and clinical response to immune checkpoint inhibitors in patients with advanced cancer

Background The gut microbiome is associated with the immune function of the host. No consensus has been reached regarding to the association between microbiota and the treatment response to immune checkpoint inhibitor (ICI). This study is designed to explore the relationship between gut microbiome composition and clinical outcomes in patients with advanced cancer treated with ICI. Methods Fifty patients were enrolled in this study. Fecal samples were collected at the baseline, 3 months after treatment and when disease progression was noted. To explore the gut microbiota as a potential predictive biomarker for immunotherapy, 16S ribosome RNA gene sequencing was used to analyze the gut microbiota profiles. Peripheral immunity parameters were determined by multicolor flow cytometry and cytokine array. Alpha-diversity of healthy individuals was used as a cut-off. Results When subgrouping patients into benefiter and non-benefiter according to the clinical response assessed, non-benefiter patients harbored lower alpha-diversity of gut microbiome at the baseline. Patients with low microbiome diversity had poor progression-free survival (HR=0.569, p=0.219) when compared to those with high diversity. Compositional difference was observed between the two groups as well with the enrichment of g_Fusicatenibacter in benefiters whereas f_Veillonellaceae enriched in non-benefiters. Analysis of immune responses using multicolor flow cytometry revealed that patients with a high diversity of gut microbiota had decreased CD4+/CD25+/FoxP3+ regulatory T cells in response to ICI. After ICI treatment the CD4/CD8 ratio of PBMCs was decreased in clinical benefiter. The serum MIF and CXCL12 levels were decreased in clinical benefiter. Conclusions Low alpha diversity of the gut microbiota is associated with poor response to immune checkpoint inhibitors in patients with advanced cancer. Further confirmation in the clinical trials is warranted. Acknowledgements The authors thank all the members of the Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, for their invaluable help. The study and data collection processes were funded by the grants to John WC Chang from Chang Gung Memorial Hospital (Grant No. CIRPG3H0061~2). Ethics Approval The study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, approval number 201801261B0. Consent Written informed consent was obtained from the patients for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.