1. Engagement of sialylated glycans with Siglec receptors on suppressive myeloid cells inhibits anticancer immunity via CCL2.
- Author
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Wieboldt R, Sandholzer M, Carlini E, Lin CW, Börsch A, Zingg A, Lardinois D, Herzig P, Don L, Zippelius A, Läubli H, and Mantuano NR
- Subjects
- Animals, Humans, Mice, Mice, Knockout, T-Lymphocytes immunology, T-Lymphocytes metabolism, Cell Line, Tumor, Lung Neoplasms immunology, Lung Neoplasms pathology, N-Acetylneuraminic Acid metabolism, Sialic Acid Binding Immunoglobulin-like Lectins metabolism, Polysaccharides metabolism, Myeloid-Derived Suppressor Cells immunology, Myeloid-Derived Suppressor Cells metabolism, Chemokine CCL2 metabolism, Mice, Inbred C57BL
- Abstract
The overexpression of sialic acids on glycans, called hypersialylation, is a common alteration found in cancer cells. Sialylated glycans can enhance immune evasion by interacting with sialic acid-binding immunoglobulin-like lectin (Siglec) receptors on tumor-infiltrating immune cells. Here, we investigated the effect of sialylated glycans and their interaction with Siglec receptors on myeloid-derived suppressor cells (MDSCs). We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors and are highly sialylated. In murine cancer models of emergency myelopoiesis, Siglec-E knockout in myeloid cells resulted in prolonged survival and increased tumor infiltration of activated T cells. Targeting suppressive myeloid cells by blocking Siglec receptors or desialylation strongly reduced their suppressive potential. We further identified CCL2 as a mediator involved in T-cell suppression upon interaction between sialoglycans and Siglec receptors on MDSCs. Our results demonstrated that sialylated glycans inhibit anticancer immunity by modulating CCL2 expression., (© 2024. The Author(s).)
- Published
- 2024
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