Abstract A027: Aberrant glycosylation in mPDAC cells is associated with increased recruitment of immunosuppressive cells

Abstract

Abstract Tumor associated-glycan Tn antigen (aGalNAc-a-O-Ser/Thr) is associated with poor prognosis in various solid tumors. However, the mechanisms that Tn antigen promotes tumorigenesis is incompletely understood. Here, we generated Tn antigen-expressing murine pancreatic ductal adenocarcinoma (mPDAC) tumor cell lines through CRISPR/Cas9-mediated knockout of the C1galt1c1 gene. Tn antigen expressing mPDAC cell lines exhibited increased in vitro proliferation and migration compared to parental controls. RNA sequencing revealed that loss of C1galt1c1 in mPDAC cells correlated with increased expression of myeloid recruitment and differentiation genes, IL34 and Lif. Additionally, C1galt1c1 knockout mPDAC cells implanted into mice led to accelerated tumor growth and increased tumor infiltration of myeloid-derived suppressor cells and neutrophils as determined by flow cytometry and scRNAseq. Interestingly, surface expression of a binding partner of Tn antigen, macrophage galactose N-acetyl galactosamine specific lectin 2 (Mgl2), was decreased in the infiltrate of C1galt1c1 knockout tumors suggesting a role for the Mgl2-Tn interaction in tumor progression. Together, our data indicate that expression of Tn antigen on tumor cells promotes an immunosuppressive microenvironment in mPDAC. Citation Format: Shawna Brookens, David Degaramo, Kiesha Wilson, Wilder Condori Obregon, Mitzi Nagarkatti, Avery Posey Jr.. Aberrant glycosylation in mPDAC cells is associated with increased recruitment of immunosuppressive cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A027.