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Published on: October 17, 2025
Sorafenib induces autophagy and suppresses activation of human macrophage
Jiunn-Chang Lin1, Chien-Liang Liu, Jie-Jen Lee
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Background:
Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity.
Materials And Methods:
Macrophages were derived from sorted CD14(+) monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA.
Results:
We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF-α nor TGF-β, was reduced by sorafenib.
Conclusion:
Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.
Insights
Sorafenib, a cancer drug, induces autophagy and alters human macrophage function. This study reveals its impact on innate immunity cells, affecting their viability and antigen expression.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Sorafenib is a multi-kinase inhibitor used for advanced cancers.
- It is known to modulate dendritic cells.
- This study investigates sorafenib's effects on macrophages, key innate immunity cells.
Purpose of the Study:
- To examine the effects of sorafenib on human macrophages.
- To understand sorafenib's impact on macrophage autophagy and function.
Main Methods:
- Macrophages were derived from human peripheral blood monocytes.
- Cell viability, surface antigens, and autophagy markers (LC-3B lipidation, autophagosome accumulation) were assessed.
- Macrophage function (co-stimulatory molecule expression, phagocytosis, ROS production, cytokine secretion) was evaluated.
Main Results:
- Sorafenib inhibited macrophage viability and induced autophagy.
- Autophagy was confirmed by morphological changes and molecular markers.
- Sorafenib reduced co-stimulatory molecule CD80 expression, phagocytosis, ROS production, and IL-10 secretion.
Conclusions:
- Sorafenib induces autophagy in human macrophages.
- Sorafenib modulates human macrophage function, impacting their immune response.
- These findings highlight sorafenib's dual role as a therapeutic agent and immune modulator.
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