A selective IDO1 inhibitor, KHK2455, improves efficacy of PD-L1 blockade by modulating both innate and adaptive immunity in a mouse melanoma model.

ABSTRACT: Indoleamine 2,3-dioxygenase 1 (IDO1) facilitates tumor progression by catabolizing tryptophan into kynurenine (Kyn). While KHK2455, a selective IDO1 inhibitor, reduced Kyn levels in mouse tumors and plasma, it did not exert the expected antitumor activity in a mouse melanoma model. However, when combined with programmed death-ligand 1 (PD-L1) blockade, KHK2455 demonstrated enhanced antitumor effects compared with PD-L1 blockade alone. This study investigated the effects of IDO1 inhibition on the tumor microenvironment and mechanisms underlying the enhanced antitumor effects of combining IDO1 inhibition with PD-L1 blockade. PD-L1 blockade upregulated the pathways related to adaptive immunity including T-helper cells type 1 and 2 (Th1 and Th2) rather than innate immunity. On the other hand,

SUBMITTER: Saito M 

PROVIDER: S-EPMC12717313 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature