Abstract 1576: The heterogeneity between pancreatic ductal adenocarcinoma with & without lymphovascular invasion

Abstract

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant solid tumors, with a five-year survival rate less than 10%. Lymphovascular invasion (LVI) is a poor prognostic indicator for PDAC, yet the difference between tumors with or without LVI is unclear. Methods We used scRNA-seq analysis on the PDAC tissue of 24 patients obtained from the National Genomics Data Center (Project number: PRJCA001063) to compare T-cell, macrophage, & cancer-associated fibroblast (CAF) heterogeneity between LVI-positive & LVI-negative PDAC. To validate the scRNA-seq results, complementary techniques, including multiple immunofluorescence assays & flow cytometry, were used. Additionally, we analyzed the characteristics of LVI-positive PDAC tumor cells. Results LVI-positive PDAC thrives in an immunosuppressive microenvironment. We discovered that CD8+ T cells were more deficient in LVI-positive PDAC than in LVI-negative PDAC. Furthermore, the effective & cytotoxic markers (such as GZMB & IFN-γ) of CD8+ T cells also decreased in LVI-positive PDAC. M2 macrophage polarization was found to be higher in LVI-positive PDAC compared to LVI-negative PDAC. In addition, we discovered a more fibrotic TME signature in LVI-positive PDAC. LVI-positive tumor cells, in particular, had a mesenchymal transition phenotype & a hypoxic microenvironment. Conclusions This study adds to our understanding of the intricate heterogeneity seen in LVI-positive PDAC. It sheds light on the distinct characteristics of LVI-positive PDAC & advances our understanding of its underlying biology. Citation Format: Yiping Zou, Yongjie Xie, Song Gao, Tianxing Zhou, Jun Yu, Jihui Hao. The heterogeneity between pancreatic ductal adenocarcinoma with & without lymphovascular invasion [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(6_Suppl):Abstract nr 1576.