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ZNF207 promotes hepatocellular carcinoma by reprogramming kynurenine metabolism and inhibiting CD8+ T cell infiltration

ABSTRACT: Bioinformatic analysis identified ZNF207 as an immunosuppressive molecule in HCC. P53R249S mutation and hypoxia synergistically elevated ZNF207 expression. Silencing ZNF207 affected tumor growth in normal mice, but not in immunodeficient mice. Flow cytometry analysis showed increased proportion of CD8+ T cells in tumor tissues while exhaustion decreased after knocking down ZNF207. Mechanism studies showed that CX3CL1 was involved in the chemotaxis of CD8+ T cells, and ZNF207 regulated kynurenine production through transcriptional regulation of IDO1, then promoting the exhaustion of CD8+ T cells. High expression of ZNF207 showed a lower response rate to immunotherapy. In vivo experiments also confirmed the efficacy of ZNF207 knockdown combined with PD1 monoclonal antibody was better than PD1 alone.

ORGANISM(S): Mus musculus

PROVIDER: GSE167935 | GEO | 2022/03/16

REPOSITORIES: GEO

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