Cancer is increasingly becoming a rising cause of mortality worldwide. Microbiota, both within the gut and tumors, has emerged as a significant player influencing tumor growth and responses to therapies. The tumor niche provides a privileged microenvironment for microbial colonization. Recent evidence links microbiota and pancreatic tumorigenesis. Pancreatic ductal adenocarcinoma (PDAC), is an aggressive cancer surrounded by a highly immuno-suppressive tumor microenvironment (TME) which limits efficacy of most available therapies. We have previously reported that rare long-term survival in pancreatic cancer is associated with an intratumoral microbial signature which correlates with enhanced TME immunoactivation, suggestive of microbial mediated immune cell recruitment. A gut-to-tumor microbial crosstalk was also found in a human-to-mouse Fecal Microbiota Transplant (FMT) tumor model. While we have identified the vital role of microbiota in affecting tumor immunity, there is still a gap of knowledge about local microbial interactions within TME. Deeper understanding of the microbial mediated events that are triggered and follow PDAC development, which act to induce and support tumor growth, would provide us with potential novel targets that could be blocked to reverse PDAC immunosuppression and tumor growth. To interrogate the features of the pancreatic tumor microbial niche, we performed spatial co-detection of microbial and host targets to identify the cellular compartment which interacts with microbes inside the TME in clinical samples. We developed novel qualitative and quantitative imaging methodologies for evaluating crosstalk between the host and microbes. We also evaluated the effect of microbial burden on transcriptomic changes in host cells through multiple spatial sequencing approaches. Overall, we dissect the functional role of microbes in orchestrating TME organization and their effect on tumor signaling.

Citation Format: Vidhi Chandra, Hajar Rajaei, Seyda Baydogan, Javier Gomez, Sammy Ferri-Borgogno, Anirban Maitra, Erick Riquelme, Ismet Sahin, Jared Burks, Michael Kim, Florencia McAllister. Interrogating host-intratumoral microbial interactions in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5918.