Myeloid cell-cycle-related-kinase drives tumor immunosuppression in hepatocellular carcinoma
نویسندگان
چکیده
Abstract Myeloid-derived suppressor cell (MDSC) comprises a heterogeneous population of immature myeloid cells featured by potent immunosuppression. We have uncovered significant role hepatoma-intrinsic cyclin-dependent-kinase 20 (CDK20), or cell-cycle-related-kinase (CCRK) in promoting tumor progression and immunotherapy resistance hepatocellular carcinoma (HCC). As emerging evidence has highlighted the importance immune intrinsic CDKs, we further explored potentials CCRK expressions functions different from HCC-bearing mice patients. Of note, specific overexpression MDSCs but not lymphocytes, which functioned regulating MDSC proliferation, immunosuppression, differentiation. Intratumoral injection bone-marrow-derived with Ccrkknockdown resulted impaired tumorigenicity, accompanied increased CD8 +T responses. Mechanistically, upregulation was functional associated IL-6-mediated expansion Inhibition turn suppressed STAT3 to revert E4-binding protein 4-dependent transcriptional alterations. Using transgenic mouse bearing Ccrk-indel mutation (Ccrkindel/indel), found that Ccrksignal reprogramed pro-tumoral into an antitumoral phenotype, resulting suppression growth our established HCC orthotopic models. also showed patient-derived MDSCs, findings study only unravel mechanistic insights maintenance offer novel therapeutic kinase-target therapies. The project is supported RGC/GRF14108219. Supported grants general research fund (GRF)/research council (RGC) Hong Kong, 14108219.
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.84.01