Abstract PO-103: Cellular origin influences immune microenvironment in a pancreatic cancer mouse model with loss of Pten and activation of Kras

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of merely 9%. Although mouse studies in the past decade have made progress towards a better understanding of how PDAC cellular origin affects tumorigenesis, there hasn’t been study on the immune microenvironment differences between precursor lesions and PDAC derived from acinar and ductal cells. Following our previous study that showed loss of Pten with oncogenic KrasG12D mutations in the ductal cells (KPtenDuct/+) resulted the formation of intraductal papillary mucinous neoplasias (IPMN) as the precursor lesion in mice, we further found siminar mutations in the acinar cells (KPtenAcinar/+) formed pancreatic intraepithelial neoplasia (PanIN) instead. We subsequently used the KPtenDuct/+ and KPtenAcinar/+ models to elucidate the effect of cellular origin on the immune microenvironment by performing immunohistochemistry. We looked at immune cell infiltration densities between precursor lesions and PDAC derived from KPtenDuct/+ and KPtenAcinar/+ models and will present the data during the conference. Additionally, macrophages polarized by conditioned media derived from KPtenDuct/+ and KPtenAcinar/+ PDAC cells showed distinctive polarization status, indicating cellular origin could result in PDAC with different cytokine and chemokine profiles that affect the immune microenvironment. Our study is the first to directly compare immune cell population between acinar- and ductal-derived PDAC originating from different types of precursor lesions with the same genetic background. Our study suggests the potential role of cellular origin on influencing PDAC immune heterogeneity. Citation Format: Yan Dou, Wesley Hunt, Justin Chhuor, Farnaz Taghizadeh, Atefeh Samani, Karnjit Sarai, Claire Dubois, David F. Schaeffer, Maike Sander, Janel L. Kopp. Cellular origin influences immune microenvironment in a pancreatic cancer mouse model with loss of Pten and activation of Kras [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-103.