Sorafenib enhanced the function of myeloid-derived suppressor cells in hepatocellular carcinoma by facilitating PPARα-mediated fatty acid oxidation.

ABSTRACT:

Background

Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC), faces resistance issues, partly due to myeloid-derived suppressor cells (MDSCs) that enhance immunosuppression in the tumor microenvironment (TME).

Methods

Various murine HCC cell lines and MDSCs were used in a series of in vitro and in vivo experiments. These included subcutaneous tumor models, cell viability assays, flow cytometry, immunohistochemistry, and RNA sequencing. MDSCs were analyzed for chemotaxis, immunosuppressive functions, fatty acid oxidation (FAO), and PPARα expression. The impact of sorafenib on tumor growth, MDSC infiltration, differentiation, and immunosuppressive function was assessed, alongside the modulation of these processes by PPARα.

Results

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SUBMITTER: Li C 

PROVIDER: S-EPMC11773820 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature