IDO1 inhibitor enhances the effectiveness of PD-1 blockade in microsatellite stable colorectal cancer by promoting macrophage pro-inflammatory phenotype polarization.

ABSTRACT: Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets. In vivo experiments demonstrated that the combination of IDO1 inhibition and PD-1 blockade significantly reduced tumor growth and increased immune cell infiltration, particularly pro-inflammatory macrophages and CD8+ T cells. IDO1 knockdown in CRC cell lines impaired tolerance to interferon-γ and increas

SUBMITTER: Guangzhao L 

PROVIDER: S-EPMC11699167 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature