Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment

Table 2 Current results for the effect of sorafenib on TAMs in HCC

Model	Dosage	Conclusion	References
Murine HCC cell line HCA-1	50 mg/kg	Sorafenib induces polarization towards a pro-immunosuppressive environment and M2 accumulation	[33]
Macrophages from human HCC tissue	1.2 μg/ml	Sorafenib revert the immunosuppressive effect of TAMs	[57]
In vivo: iAST mice	90 mg/kg 60 mg/kg 30 mg/kg 10 mg/kg	Sorafenib upregulates proinflammatory cytokine secretion and induce pyroptosis in macrophage	[58]
Monocyte-derived M1 and M2 macrophage cultures	1.2 μg/ml 2.5 μg/ml 5.0 μg/ml	Sorafenib revert the alternative macrophage polarization	[67]
In vitro: CSF-1 (M1) or GMCSF (M2) maturated monocyte-derived macrophages In vivo: patients with confirmed HCC	In vitro: 1.2 μg/ml 2.5 μg/ml 5.0 μg/ml In vivo: 800 mg/day	Sorafenib revert the alternative macrophage polarization, shifting the phenotype towards the M1-polarized state in vitro, and partially inhibits macrophage activation in vivo	[68]
C57BL/6 mice bearing tumour of approximately 50 mm³ in volume	30 mg/kg	Sorafenib induces the macrophage polarization in vivo but not in vitro	[69]

ISSN: 1475-2867