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Abstract

Breast cancer is the leading cause of cancer-related deaths in females. In the breast tumor microenvironment, tumor infiltrating leukocyte cells play a crucial role in eliciting tumor cell death. Immunotherapy has emerged as a new therapeutic option to treat breast cancer by stimulating the anticancer activity of immune cells. To improve on current immunotherapy strategies, we must identify new immune-inhibitory factors in breast cancer that can be targeted with blocking therapeutics. Recently, it was found that expression of the glycan polysialic acid on tumor-associated leukocytes is prognostically significant in breast cancer patients. Polysialic acid regulation or function in the human immune system has not been researched in depth, and further studies are required to understand how polysialic acid regulates the anticancer activity of immune cells. While glycans play a central role in regulating immune recognition, the role of polysialic acid specifically in driving breast cancer immune evasion is comparatively understudied. We propose that polysialic acid plays a role in the anticancer immune cell response. In this study, we performed extensive immunophenotyping of polysialic acid expression on immune cell subsets using flow cytometry. Monocytes, B-cells and naïve T-cells expressed low levels of polysialic acid. However, stimulated T-cells expressed polysialic acid at higher levels after one week of activation, and the expression of polysialic acid decreased by two weeks. In activated T-cells, NCAM was found to be polysialylated as well as other unknown protein carriers, as assessed by western blot and flow cytometry. Furthermore, functional killing assays to assess the role of polysialic acid in immune-mediated anticancer function found that T-cell cytotoxicity is not regulated by polysialic acid, however data suggests macrophage phagocytosis is impacted by polysialic acid.