Abstract B082: Viable pancreatic tumor resident microbes constrain antigen presentation and therapy responses

Abstract

Tumor resident microbes are key components of the tumor microenvironment. However, standard microbial profiling techniques lack subcellular resolution and functional validation. Visualization of microbial compartmentalization in situ across gastrointestinal tumors revealed microbial enrichment within tumor cells. Spatial transcriptomics based on microbial presence in human pancreatic ductal adenocarcinoma (PDAC) identified microbial regulation of autophagy. Multiplexed culturomics analysis of pancreatic tumors and adjacent tissue identified heterogeneous viable bacterial species with enrichment of Klebsiella pneumoniae (K.p.) within tumors. K.p. specific spatial analyses linked it to immune evasion through downregulation of antigen presentation. Mechanistic interrogation of K.p in murine models revealed induction of tumor growth and downregulation of antigen presentation that led to reduced therapeutic efficacy. Finally, we identified non-invasive microbial markers based on K.p. antibody reactome that predicted clinical outcomes. In summary, multiple orthogonal approaches provide mechanistic and functional insights on how tumor-resident microbes influence PDAC biology.