Abstract
Abstract Pancreatic cancer (PC) continues to be a challenge for today’s therapeutics, with a meager 5-year survival rate of 11%. 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 that contributes to tumor cells’ survival and proliferation. Infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME) often cause this inflammation. Previously we have determined that inflammation and CXCR2 ligand expression increases with pancreatic ductal adenocarcinoma (PDAC) progression. In the present study, we examined the role of neutrophil recruitment in PDAC progression using Kras-dependent KC and KPC murine models. Our data suggest a positive association between tumor-associated neutrophils (TANs) and PDAC progression. Furthermore, the frequency of neutrophil extracellular traps (NETs) also increased as the disease progressed. In vitro, we observed PDAC cell condition-media enhanced survival of neutrophils in a concentration-dependent manner. Moreover, increased survival was associated with disease aggressiveness and therapy resistance. Additionally, we observed that PDAC-conditioned media modulated the expression of immunoregulatory cytokines and chemokines in neutrophils. Together, our data suggest that increased recruitment of TANs supports PDAC progression, and PDAC cell-neutrophil interaction modulates neutrophil survival and immunoregulatory phenotype. Citation Format: Reegan Sturgeon, Paran Goel, Caitlin Molczyk, Surindar K. Batra, Rakesh 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 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1348.
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