biostudies-literatureFriedman DJNIAID NIH HHSHHS | NIH | National Institute of Allergy and Infectious DiseasesNCI NIH HHSMayo Clinic Center for Biomedical Discovery1845-1850https://www.ebi.ac.uk/biostudies/studies/S-EPMC9012686biostudies-literatureUnknown208(8)Inhibitory receptors have a critical role in the regulation of immunity. Siglecs are a family of primarily inhibitory receptors expressed by immune cells that recognize specific sialic acid modifications on cell surface glycans. Many tumors have increased sialic acid incorporation. Overexpression of the sialyltransferase ST8Sia6 on tumors led to altered immune responses and increased tumor growth. In this study, we examined the role of ST8Sia6 on immune cells in regulating antitumor immunity. ST8Sia6 knockout mice had an enhanced immune response to tumors. The loss of ST8Sia6 promoted an enhanced intratumoral activation of macrophages and dendritic cells, including upregulation of CD40. Intratumoral regulatory T cells exhibited a more inflammatory phenotype in ST8Sia6 knockout mice. Using Journal of immunology (Baltimore, Md. : 1950)Cutting Edge: Enhanced Antitumor Immunity in ST8Sia6 Knockout Mice.PMC9012686N/AP30 CA015083T32AI007425R01CA243545T32 AI007425R01 CA243545Theodore KKizerwetter MShapiro MJDong HShapiro VSFriedman DJBelmonte PRajcula MKim Lee HSfalseCutting Edge: Enhanced Antitumor Immunity in ST8Sia6 Knockout Mice.Inhibitory receptors have a critical role in the regulation of immunity. Siglecs are a family of primarily inhibitory receptors expressed by immune cells that recognize specific sialic acid modifications on cell surface glycans. Many tumors have increased sialic acid incorporation. Overexpression of the sialyltransferase ST8Sia6 on tumors led to altered immune responses and increased tumor growth. In this study, we examined the role of ST8Sia6 on immune cells in regulating antitumor immunity. ST8Sia6 knockout mice had an enhanced immune response to tumors. The loss of ST8Sia6 promoted an enhanced intratumoral activation of macrophages and dendritic cells, including upregulation of CD40. Intratumoral regulatory T cells exhibited a more inflammatory phenotype in ST8Sia6 knockout mice. Using 2022-01-01T00:00:00Z2022 Apr2025-04-21T22:50:39.472Z2025-04-05T18:59:34.322ZS-EPMC90126863537974610.4049/jimmunol.2101165