Abstract C076: Bacterial dysbiosis and its association with pancreatic cancer progression and poor survival

Abstract

Abstract Bacterial dysbiosis is emerging as an accomplice to carcinogenesis and is associated with pancreatic cancer progression and poorer survival. We found that gut bacteria can directly access the pancreas, and pancreatic tumors harbor a unique microbiome that differs from that of the healthy pancreas. We have also found that the tumor-associated microbiome regulates pancreatic cancer progression by skewing tumor-infiltrating immune cells towards an immunosuppressive phenotype. However, the exact mechanisms via which bacteria regulate immune cell function is still unknown. Inflammatory signaling by cancer cells and stromal cells in the tumor microenvironment has been shown to effectively regulate immune cell infiltration and differentiation. Our data suggests that pathogenic bacteria in the pancreatic tumor microenvironment can directly engage with pancreatic epithelial cells inducing proliferation and an inflammatory response. Specifically, the dominant Proteobacteria in the pancreatic tumor microenvironment induces the production of many pro-tumorigenic cytokines, such as IL-8 and IL-6, from cancer cells and pancreatic epithelial cells. Furthermore, we have found that pancreatic tumor- associated bacteria skews fibroblast differentiation towards an inflammatory, tumor-promoting phenotype. These findings show that pathogenetic tumor-associated bacteria can modulate the epithelial and stromal compartments in the pancreatic tumor microenvironment, thereby serving as mediators of tumorigenesis. Our results delineate the mechanisms via which microbes interface with the non-immune cell compartment in the tumor microenvironment and provide insight into therapeutic strategies for gut microbial modulation in treating pancreatic cancer. Citation Format: Holly B. Attebury. Bacterial dysbiosis and its association with pancreatic cancer progression and poor survival [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C076.