Ligand-Receptor interactions of galectin-9 and VISTA suppress human T lymphocyte cytotoxic activity

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),