Multimodal immune phenotyping reveals microbial-T cell interactions that shape pancreatic cancer
Year: 2024
Type: article
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.
Source: Cell Reports Medicine
Authors: 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 Giannone, Sarah M. Shin, Erin M. Coyne, Alexei Hernandez, Nicole E. Gross, Soren Charmsaz, Won Jin Ho, Jae W. Lee, Gregory L. Beatty
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: American Association for Cancer Research, Cancer Research Institute, Pancreatic Cancer Action Network, Lustgarten Foundation, University of Pennsylvania, Mark Foundation For Cancer Research, Incyte, National Institutes of Health, Stand Up To Cancer, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1733189847, Disrupting the immune and drug-privileged microenvironment in pancreas cancer, Penn Resource-based Center to Support and Translate Skin DiseasesResearch, G2850719307, Immunophenotype Integration for Monitoring T Cell Dynamics in Pancreatic Cancers, G316567086, G3173929358, G3764027029, G432566759, G4424250656, G4492193758, G5224084475, G5594956475, G5671712028, G7334819345, G9000015332, G9000091755, G9000126776, G9000142446, G9000217448, G9000323715, Center for 3D Imaging in Cancer Cell Biology
OpenAlex ID: W4391431978