Multimodal immune phenotyping reveals microbial-T cell interactions that shape pancreatic cancer

Abstract

Microbes are an integral component of the tumor microenvironment. However, determinants of microbial presence remain ill-defined. Here, using spatial-profiling technologies, we show that bacterial and immune cell heterogeneity are spatially coupled. Mouse models of pancreatic cancer recapitulate the immune-microbial spatial coupling seen in humans. Distinct intra-tumoral niches are defined by Tcells, with Tcell-enriched and Tcell-poor regions displaying unique bacterial communities that are associated with immunologically active and quiescent phenotypes, respectively, but are independent of the gut microbiome. Depletion of intra-tumoral bacteria slows tumor growth in Tcell-poor tumors and alters the phenotype and presence of myeloid and B cells in Tcell-enriched tumors but does not affect Tcell infiltration. In contrast, Tcell depletion disrupts the immunological state of tumors and reduces intra-tumoral bacteria. Our results establish a coupling between microbes and Tcells in cancer wherein spatially defined immune-microbial communities differentially influence tumor biology.