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Investigate how sorafenib treatment influences myeloid-derived suppressor cell activity and lipid metabolism to drive therapy resistance in hepatocellular carcinoma.

January 28, 2025Molecular CancerOpen Access

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

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Authors

CLChunxiao LiQingdao University LXLiting XiongPeking University YYYuhan YangHubei University of Medicine

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Implication

Preclinical study reveals that sorafenib enhances immunosuppressive myeloid cell activity via PPARα-driven fatty acid oxidation in liver cancer, suggesting strategies to overcome drug resistance.

Key Points

Investigate how sorafenib treatment influences myeloid-derived suppressor cell activity and lipid metabolism to drive therapy resistance in hepatocellular carcinoma.
Evaluated murine hepatocellular carcinoma cell lines and MDSCs using in vitro assays and in vivo subcutaneous mouse tumor models.
Assessed cell viability, flow cytometry, immunohistochemistry, RNA sequencing, chemotaxis, and fatty acid oxidation under regular and high-fat diets.
Analyzed the effects of genetic PPARα deletion, pharmacological PPARα inhibition, and CCR2 blockade in combination with sorafenib.
Sorafenib promoted MDSC infiltration via CCR2 signaling and enhanced MDSC immunosuppressive function through PPARα-mediated fatty acid uptake and oxidation.
Mice fed a high-fat diet exhibited worse outcomes during sorafenib therapy, whereas genetic deletion or pharmacological inhibition of PPARα synergistically suppressed tumor growth when combined with sorafenib.
Sorafenib impaired macrophage differentiation by upregulating PPARα expression and suppressing the PU.1-CSF1R signaling pathway.

Cite This Study

Li et al. (2025) studied this question.

synapsesocial.com/papers/6aae32102335b257170d7ec0 https://doi.org/10.1186/s12943-025-02238-5

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Implication

Preclinical study reveals that sorafenib enhances immunosuppressive myeloid cell activity via PPARα-driven fatty acid oxidation in liver cancer, suggesting strategies to overcome drug resistance.

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

Discussion

Member takes

Implication

Key Points

Cite This Study

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

Discussion

Member takes

Implication

Key Points

Cite This Study

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