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Abstract Pancreatic cancer (PC) continues to be a challenge for today’s therapeutics, with a meager 5-year survival rate of 12%. Due to the pancreas’ location, patients often receive diagnosis late, leaving them with limited treatment options. Often, they fail to respond to chemotherapy regimens or develop resistance to those therapies. Tumor-promoting inflammation is a hallmark of cancer, contributing to tumor cells’ survival and proliferation. Infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME) often cause this inflammation. My lab has previously linked increases in pancreatic ductal adenocarcinoma (PDAC) progression and chemotherapy resistance to inflammation and the CXCR2 pathway. In the present study, we examined the role of neutrophil recruitment in PDAC progression using patient samples and KRAS-dependent KC and KPC murine models. Our data suggest a positive association between tumor-associated neutrophils (TANs) and PDAC progression. In vitro, we observed neutrophil-PDAC interaction enhancing the survival of both neutrophils and PDAC cell lines. Moreover, this survival was mediated by cellular aggressiveness and therapy resistance. Concerning survival, we saw increased expression of anti-apoptotic genes in the neutrophils upon PDAC cancer cell conditioned media treatment. We also observed modulated expression of immunoregulatory molecules. Our data suggest that increased recruitment of TANs supports PDAC progression and survival, and PDAC cell-neutrophil interaction modulates neutrophil survival and immunoregulatory phenotype. Citation Format: Reegan Sturgeon, Esther Johnson, Caitlin Molczyk, Paran Goel, Parker Tinsley, Lauren Abrahams, Michael Maher, Rakesh K. Singh. Neutrophil pro-tumorigenic role in progression and therapy resistance in pancreatic ductal adenocarcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1583.
Sturgeon et al. (Fri,) studied this question.