1276 Targeting sialic acid on cancer-associated stromal cells modulates macrophage phenotype and phagocytosis in colorectal cancer

作者：Norashikin Zakaria, Aoise O’Neill, Lei Lei, Anastasija Walsh, Jenny Chee, Li Peng, Lizhi Cao, Seán O. Hynes, Aisling Hogan, Oliver Treacy, Aideen E. Ryan · 发表于：Regular and Young Investigator Award Abstracts · 年份：2025 · DOI：10.1136/jitc-2025-sitc2025.1276 · 研究领域：Glycosylation and Glycoproteins Research、Immune cells in cancer、Cancer Research and Treatments

Background Stromal-rich CMS4 colorectal cancer (CRC), is associated with high stromal burden, poor immune cell infiltration, poor response to anti-cancer therapies leading to poor prognosis. 1 Immune checkpoint inhibitors (ICIs) have limited impact on this tumor, highlighting the need for new therapy. Emerging studies have highlighted that stromal cells in stromal-rich tumors, including CRC, are highly sialylated and immunosuppressive.2 3 This study investigates the effect of targeting stromal cells sialylation in modulating macrophage phenotype and function in CRC.Methods Sialic acid and Siglec-7/9/10 ligand expression on tumor-conditioned MSCs and CAFs were evaluated using lectins (SNA-I, MAL-II) and Siglec-7/9/10 fc chimera, and Siglec-7/9/10 were measured on immune cells, all by flow cytometry. Ex vivo human monocyte derived and murine bone marrow-derived macrophage were co-culture with stromal cells, macrophage polarisation and phagocytosis were measured by flow cytometry and Incucyte. In vivo syngeneic immunogenic subcutaneous CT26 mouse tumor model with co-injection of MSCs were performed and the changes in macrophage macrophage phenotype within the tumor, draining lymph nodes (DLNs), and spleen were evaluated using flow cytometry.Results We observed that MSC TCS and CAF in CRC tumors are highly sialylated and significantly overexpressed Siglec-10 ligand compared to cancer cells. In co-culture experiments, MSCTCS and CAFs induced Siglec-10 expression on macrophages and...