(548f) An Immunoinhibitory Glycocalyx Signature Associates with Breast Cancer Aggression

Breast cancer is a leading cause of cancer death worldwide. To improve treatment, it is important to understand what features of breast tumors associate with aggression and mortality. One of these features is the glycocalyx, the outermost layer of glycoproteins and glycolipids that decorate all cell surfaces and is dysregulated in cancer. The cancer cell glycocalyx in breast cancer has altered composition and structure that increases proliferation and enhances immune evasion. However, it is unknown how these single-cell changes manifest throughout the tumor tissue. To better understand tissue-level features of the cancer cell glycocalyx, we used a combination of immunostaining, bioinformatics, and mass spectrometry. We focused our characterization of the cancer cell glycocalyx on sialic acid, a terminal sugar that is increased on tumor cells and is a necessary component of the ligands for immunosuppressive receptors called Siglecs. We confirmed that overall sialic acid content of the cancer cell glycocalyx is increased in breast tumors, relative to healthy breast epithelial cells. In addition, we found that Siglec ligands are also increased in the cancer cell glycocalyx, suggesting immunosuppressive activity. Further, we found that myeloid cells, especially macrophages, were the primary cell type that expresses Siglecs in human breast tumors across all subtypes. Finally, we discovered associations between an immunosuppressive glycocalyx, immune infiltration, and tumor aggression. Taken together, this study identifies a glycocalyx signature of breast cancer aggression and provides new information for stratifying patients for treatment.