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D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells

Hammon, Kathrin ; Renner, Kathrin ; Althammer, Michael ; Voll, Florian ; Babl, Nathalie ; Decking, Sonja-Maria ; Siska, Peter J. ; Matos, Carina ; Conejo, Zugey Elizabeth Cárdenas ; Mendes, Karina ; Einwag, Friederike ; Siegmund, Heiko ; Iberl, Sabine ; Berger, Raffaela S. ; Dettmer, Katja ; Schoenmehl, Rebecca ; Brochhausen, Christoph ; Herr, Wolfgang ; Oefner, Peter J. ; Rehli, Michael ; Thomas, Simone ; Kreutz, Marina



Abstract

D-2-hydroxyglutarate (D-2-HG) accumulates in primary acute myeloid leukemia (AML) patients with mutated isocitrate dehydrogenase (IDH) and other malignancies. D-2-HG suppresses antitumor T cell immunity but little is known about potential effects on non-malignant myeloid cells. Here we show that D-2-HG impairs human but not murine dendritic cell (DC) differentiation, resulting in a tolerogenic ...

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