Haas, QuentinQuentinHaasMarkov, NikitaNikitaMarkovMürner, Lukas DominicLukas DominicMürnerRubino, VivianaVivianaRubinoBenjak, AndrejAndrejBenjakHaubitz, MonikaMonikaHaubitzBärlocher, Gabriela MariaGabriela MariaBärlocherNg, Kiu Yan CharlotteKiu Yan CharlotteNgMünz, ChristianChristianMünzRiether, CarstenCarstenRiether0000-0001-7512-513XOchsenbein, AdrianAdrianOchsenbeinSimon, Hans-UweHans-UweSimon0000-0002-9404-7736von Gunten, StephanStephanvon Gunten2024-10-112024-10-112022https://boris-portal.unibe.ch/handle/20.500.12422/88008While inhibitory Siglec receptors are known to regulate myeloid cells, less is known about their expression and function in lymphocytes subsets. Here we identified Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells that exhibit high functional and metabolic capacities. Seahorse analysis revealed higher basal respiration and glycolysis levels of Siglec-7+ CD8+ T cells in steady state, and particularly upon activation. Siglec-7 polarization into the T cell immune synapse was dependent on sialoglycan interactions in trans and prevented actin polarization and effective T cell responses. Siglec-7 ligands were found to be expressed on both leukemic stem cells and acute myeloid leukemia (AML) cells suggesting the occurrence of glyco-immune checkpoints for Siglec-7+ CD8+ T cells, which were found in patients' peripheral blood and bone marrow. Our findings project Siglec-7 as a glyco-immune checkpoint and therapeutic target for T cell-driven disorders and cancer.enCD8+ T cells Siglec-7 acute myeloid leukemia hypersialylation immune checkpoint sialoglycans tumor immunity and immunotherapy600 - Technology::610 - Medicine & healthSiglec-7 represents a glyco-immune checkpoint for non-exhausted effector memory CD8+ T cells with high functional and metabolic capacities.article10.48350/1736463621137610.3389/fimmu.2022.996746