Cancers, Vol. 13, Pages 1899: IDO1-Targeted Therapy Does Not Control Disease Development in the E µ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia

Cancers, Vol. 13, Pages 1899: IDO1-Targeted Therapy Does Not Control Disease Development in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia Cancers doi: 10.3390/cancers13081899 Authors: Selcen Öztürk Verena Kalter Philipp M. Roessner Murat Sunbul Martina Seiffert Indoleamine-2,3-dioxygenase 1 (IDO1), a tryptophan (Trp)-catabolizing enzyme producing metabolites such as kynurenine (Kyn), is expressed by myeloid-derived suppressor cells (MDSCs) and associated with cancer immune escape. IDO1-expressing monocytic MDSCs were shown to accumulate in patients with chronic lymphocytic leukemia (CLL) and to suppress T cell activity and induce suppressive regulatory T cells (Tregs) in vitro. In the Eµ-TCL1 mouse model of CLL, we observed a strong upregulation of IDO1 in monocytic and granulocytic MDSCs, and a significantly increased Kyn to Trp serum ratio. To explore the potential of IDO1 as a therapeutic target for CLL, we treated mice after adoptive transfer of Eµ-TCL1 leukemia cells with the IDO1 modulator 1-methyl-D-tryptophan (1-MT) which resulted in a minor reduction in leukemia development which disappeared over time. 1-MT treatment further led to a partial rescue of the immune cell changes that are induced with CLL development. Similarly, treatment of leukemic mice with the clinically investigated IDO1 inhibitor epacadostat reduced the frequency of Tregs and initially delayed CLL development slightly, an effect that was, however, lost at later time po...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research