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.
YASINSKA Inna M.;
MEYER 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;
FASLER-KAN Elizaveta;
SUMBAYEV Vadim;
2020-12-03
FRONTIERS MEDIA SA
JRC120567
1664-3224 (online),
https://publications.jrc.ec.europa.eu/repository/handle/JRC120567,
10.3389/fimmu.2020.580557 (online),
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