期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.996746
关键词
Siglec-7; CD8+T cells; acute myeloid leukemia; immune checkpoint; tumor immunity and immunotherapy; sialoglycans; hypersialylation
类别
资金
- Swiss National Science Foundation (SNSF) [310030_184757]
- Swiss Cancer League/Swiss Cancer Research [KFS-4958-02-2020]
- Palleon Pharmaceuticals Inc., Waltham MA (USA)
- Mizutani Foundation for Glycoscience
- Novartis Research Foundation
- Bern Center for Precision Medicine (BCPM)
- Swiss National Science Foundation [310030-166473, 310030_184816, 310030_204470/1, 310030L_197952/1, CRSII5_180323]
- European Union [642295]
- Russian Government Program Recruitment of the Leading Scientists into the Russian Institutions of Higher Education [075-15-2021-600]
- Cancer Research Switzerland [KFS-4962-02-2020]
- HMZ ImmunoTargET of the University of Zurich
- Cancer Research Center Zurich
- Sobek Foundation
- Swiss Vaccine Research Institute
- Swiss MS Society [2021-09]
- Roche
- Novartis
- Innosuisse [52533.1]
This study investigates the expression and function of inhibitory Siglec receptors in lymphocyte subsets. The researchers discover Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells, regulating their functional and metabolic capacities. They also find that Siglec-7 polarization into the T cell immune synapse depends on sialoglycan interactions, which prevent actin polarization and effective T cell responses. Siglec-7 ligands are observed on leukemic stem cells and acute myeloid leukemia (AML) cells, suggesting the potential therapeutic role of Siglec-7 in T cell-driven disorders and cancer.
While 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.
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