Multimodal immune phenotyping reveals microbial-T cell interactions that shape pancreatic cancer
Yan Li, Renee B. Chang, Meredith L. Stone, Devora Delman, Kelly Markowitz, Yuqing Xue, Heather Coho, Veronica M. Herrera, Joey H. Li, Liti Zhang, Shaanti Choi-Bose, Michael A. Giannone, Sarah M. Shin, Erin M. Coyne, Alexei Hernandez, Nicole Groß, Soren Charmsaz, Won Jin Ho, Jae W. Lee, Gregory L. Beatty
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 T cells, with T cell-enriched and T cell-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 T cell-poor tumors and alters the phenotype and presence of myeloid and B cells in T cell-enriched tumors but does not affect T cell infiltration. In contrast, T cell depletion disrupts the immunological state of tumors and reduces intra-tumoral bacteria. Our results establish a coupling between microbes and T cells in cancer wherein spatially defined immune-microbial communities differentially influence tumor biology.