AUTHOR=Yasinska Inna M. , Meyer N. Helge , Schlichtner Stephanie , Hussain Rohanah , Siligardi Giuliano , Casely-Hayford Maxwell , Fiedler Walter , Wellbrock Jasmin , Desmet Cloe , Calzolai Luigi , Varani Luca , Berger Steffen M. , Raap Ulrike , Gibbs Bernhard F. , Fasler-Kan Elizaveta , Sumbayev Vadim V. TITLE=Ligand-Receptor Interactions of Galectin-9 and VISTA Suppress Human T Lymphocyte Cytotoxic Activity JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.580557 DOI=10.3389/fimmu.2020.580557 ISSN=1664-3224 ABSTRACT=

Acute myeloid leukemia (AML), a blood/bone marrow cancer, is a severe and often fatal malignancy. AML cells are capable of impairing the anti-cancer activities of cytotoxic lymphoid cells. This includes the inactivation of natural killer (NK) cells and killing of T lymphocytes. Here we report for the first time that V-domain Ig-containing suppressor of T cell activation (VISTA), a protein expressed by T cells, recognizes galectin-9 secreted by AML cells as a ligand. Importantly, we found that soluble VISTA released by AML cells enhances the effect of galectin-9, most likely by forming multiprotein complexes on the surface of T cells and possibly creating a molecular barrier. These events cause changes in the plasma membrane potential of T cells leading to activation of granzyme B inside cytotoxic T cells, resulting in apoptosis.