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B23-Circular Dichroism	Ligand-receptor interactions of galectin-9 and VISTA suppress human T lymphocyte cytotoxic activity Inna M. Yasinska , N. Helge Meyer , Stephanie Schlichtner , Rohanah Hussain , Giuliano Siligardi , Maxwell Casely-Hayford , Walter Fiedler , Jasmin Wellbrock , Cloe Desmet , Luigi Calzolai , Luca Varani , Steffen M. Berger , Ulrike Raap , Bernhard F. Gibbs , Elizaveta Fasler-Kan , Vadim V. Sumbayev Frontiers In Immunology 11 DOI: 10.3389/fimmu.2020.580557 Diamond Proposal Number(s): [24509, 20755, 21202] Open Access Show Abstract ▼ 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.	Nov 2020

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