Abstract B101: Classification based on intratumoral microbiome confer the molecular characteristics and immune microenvironment in gastric cancer

Abstract Gastric cancer (GC) with the immuno-activating tumor microenvironment (TME) significantly correlated with better oncologic outcomes or response to immunotherapy. Increasing evidence suggests that intratumoral microbiome promote carcinogenesis or tumor progression by genetic instability and remodeling of the immune landscape and oncogenic signals. However, the correlation between intratumoral microbiome and genetic or immune profiling has not been clearly disclosed in GC. To capture the complexity of bacterial composition within GC and its TME, we analyzed The Cancer Microbiome Atlas (TCMA)-public data from 100 GC patients, including bacterial abundance profiles, bulk RNA sequencing, CIBERSORT, and DNA mutation in this study. Using partitioning around medoids (PAM) clustering, we classified GC microbiome structures into four distinct types based on dominant bacterial genera: Lactobacillus, Helicobacter, Prevotella, and Streptococcus. By using rcorr-based Pearson’s correlation analysis and Redundancy Analysis (RDA), we found that association of intratumor microbiome with immune cell proportion and cancer gene mutation. The Lactobacillus-dominant type exhibited both bacteria-immune cell and bacteria-bacteria interactions with upregulation of bacterial invasion of epithelial cells, and the Streptococcus-dominant type showed downregulation of gastric acid secretion pathways. While, the Prevotella-dominant type was characterized by higher abundance of activated memory CD4 T cells, CD8 T cells, M1 macrophages than other types, especially Streptococcus-dominant type, and also associated with KRAS mutations. It implies that intratumoral Prevotella-dominant type play a role of immune activation in the TME. This study demonstrated that a specific intratumoral microbiome cluster, Prevotella-dominant type, may promote immune activation of TME in patients with GC. Overall, this study provides insights into the potential impact of specialized intratumoral microbiomes on the TME in GC patients. Citation Format: Han Na Oh, Hoon Hur. Classification based on intratumoral microbiome confer the molecular characteristics and immune microenvironment in gastric cancer [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B101.