Dietary pattern and the corresponding gut microbiome in response to immunotherapy in Thai patients with advanced non-small cell lung cancer (NSCLC).

204 Background: Gut microbiota is considered a key player modulating the response to immune checkpoint inhibitors (ICI) in cancer. The effects of dietary pattern on this interaction is not well-studied. Methods: A prospective multicenter cohort of 95 patients with advanced non-small cell lung cancer (NSCLC) undergoing ICI therapy were enrolled. Stool shotgun metagenomic sequencing was performed. Three-day dietary patterns before ICI were assessed. Patients were categorized as hyperprogressive disease (HPD) if they exhibited a time to treatment failure of <2 months. All others were categorized as non-hyperprogressive disease (non-HPD). The correlation between dietary patterns, gut microbiome, and response to ICI therapy was analyzed. Results: In the multivariate analysis, high abundance of Firmicutes unclassified and the Ruminococcaceae family correlated with significantly diminished progression-free survival (PFS) with HR of 2.40 [ P=0.006] and 4.30 [ P=0.005], respectively. More specifically, within the subset of NSCLC patients treated solely with ICI therapy, high abundance of Intestinimonas and the Enterobacteriaceae family were associated with reduced PFS with HR of 2.61 [ P=0.02] and HR 3.34 [ P=0.005], respectively. In dietary pattern analysis, HPD group showed increased consumption of cholesterol, sodium, and fats beyond recommended levels compared to non-HPD group. This group also displayed a tendency towards higher food pattern scores characterized by significant intake of fat and dairy products. Conclusions: Our study revealed distinct association between the gut microbiome composition and treatment outcomes. Based on these findings, the overall composition of diet may play a pivotal role in ICI therapeutic outcomes. [Table: see text]