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

DOI
https://doi.org/10.3389/fimmu.2022.996746
Journal volume & issue
Vol. 13

Abstract

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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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