Abstract B011: Functional interrogation of the pancreatic intratumoral microbial niche reveals tumor modulation and reshaping of the microenvironment

Abstract Tumor resident microbes are a well-recognized component of the tumor microenvironment. Microbial subcellular location within different tumor types along with their functionality remains to be determined. Bulk microbial profiling techniques, however, lack subcellular and spatial transcriptomic resolution. To address these limitations, we developed advanced quantitative fluorescent imaging methodologies that allowed for visualization of microbial cellular compartmentalization across different tumor types. Furthermore, we performed spatial microbial transcriptomics at the regional and single cell levels to interrogate microbial regulation of signaling within pancreatic cancer cells. To confirm presence of viable microbes within tumors, we performed multiplexed culturomics of patient tissue samples followed by Whole Genomic Sequencing (WGS) analysis. We used in vitro co-culture assays together with in vivo animal experiments for functional biological validation. Overall, our results identified several pathways under microbial regulation within cancer cells that can drive immune evasion through impaired antigen presentation. In summary, using multiple complimentary novel methodologies we characterize the microbial niche of tumors (MiNT) that uncovers microbial regulation of host cells signaling and reshaping of the surrounding tumor microenvironment. Citation Format: Vidhi Chandra, Le Li, Seyda Baydogan, Haoyue Liu, Javier Gomez, Steven B. Maron, Daniel Carvajal-Hausdorf, Erick M. Riquelme, Mark W. Hurd, Anirban Maitra, Luis Diaz, Ismet Sahin, Jared Burks, Michael P. Kim, Florencia McAllister. Functional interrogation of the pancreatic intratumoral microbial niche reveals tumor modulation and reshaping of the microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B011.