Frontiers in Immunology (Sep 2022)
Siglec-7 represents a glyco-immune checkpoint for non-exhausted effector memory CD8+ T cells with high functional and metabolic capacities
- Quentin Haas,
- Quentin Haas,
- Nikita Markov,
- Nikita Markov,
- Lukas Muerner,
- Lukas Muerner,
- Lukas Muerner,
- Viviana Rubino,
- Viviana Rubino,
- Viviana Rubino,
- Andrej Benjak,
- Monika Haubitz,
- Monika Haubitz,
- Gabriela M. Baerlocher,
- Gabriela M. Baerlocher,
- Charlotte K. Y. Ng,
- Christian Münz,
- Carsten Riether,
- Carsten Riether,
- Adrian F. Ochsenbein,
- Adrian F. Ochsenbein,
- Hans-Uwe Simon,
- Hans-Uwe Simon,
- Hans-Uwe Simon,
- Hans-Uwe Simon,
- Stephan von Gunten,
- Stephan von Gunten
Affiliations
- Quentin Haas
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Quentin Haas
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
- Nikita Markov
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Nikita Markov
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
- Lukas Muerner
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Lukas Muerner
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
- Lukas Muerner
- Bern Center for Precision Medicine (BCPM), University of Bern, Bern, Switzerland
- Viviana Rubino
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
- Viviana Rubino
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Viviana Rubino
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Andrej Benjak
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Monika Haubitz
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Monika Haubitz
- Experimental Hematology, Department for BioMedical Research, University of Bern, Bern, Switzerland
- Gabriela M. Baerlocher
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Gabriela M. Baerlocher
- Experimental Hematology, Department for BioMedical Research, University of Bern, Bern, Switzerland
- Charlotte K. Y. Ng
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Christian Münz
- Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
- Carsten Riether
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Carsten Riether
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Adrian F. Ochsenbein
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Adrian F. Ochsenbein
- Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
- Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Hans-Uwe Simon
- Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia
- Hans-Uwe Simon
- Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
- Hans-Uwe Simon
- 0Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
- Stephan von Gunten
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Stephan von Gunten
- Bern Center for Precision Medicine (BCPM), University of Bern, Bern, Switzerland
- DOI
- https://doi.org/10.3389/fimmu.2022.996746
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
- Siglec-7
- CD8+ T cells
- acute myeloid leukemia
- immune checkpoint
- tumor immunity and immunotherapy
- sialoglycans