Therapy Combining Sorafenib and Natural Killer Cells for Hepatocellular Carcinoma: Insights from Magnetic Resonance Imaging and Histological Analyses.

Hepatocellular carcinoma (HCC) remains a significant global health issue due to its high mortality rate and resistance to standard treatments. Sorafenib, the first-line systemic therapy for unresectable HCC, shows limited effectiveness due to resistance and severe side effects. Recent studies suggest that combining sorafenib with immunotherapy, particularly natural killer (NK) cells, may improve treatment outcomes. This study examined the effectiveness of sorafenib combined with NK cells pretreated with interleukin-12 (IL-12) and interleukin-18 (IL-18) in a rat HCC model. Tumor progression and treatment outcomes were assessed using MRI and histological analysis. The results show that combination therapy significantly reduced tumor growth, increased tumor cell density, and inhibited angiogenesis and fibrosis in the tumor microenvironment. The sorafenib- and IL-12/IL-18-pretreated NK cell combination enhanced tumor inhibition by overcoming drug resistance and modulating the immune response. This study suggests that this combination therapy could be a promising strategy for treating HCC, offering both direct antitumor effects and modification of the tumor microenvironment for better clinical outcomes.