Zhang Zigeng, Yu Guangbo, Eresen Aydin, Hou Qiaoming, Webster Sha, Amirrad Farideh, Nauli Surya, Zhang Zhuoli
Department of Radiological Sciences, University of California Irvine, Irvine, CA 92617, USA.
Department of Biomedical Engineering, University of California Irvine, Irvine, CA 92617, USA.
Cancers (Basel). 2025 Feb 19;17(4):699. doi: 10.3390/cancers17040699.
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.
肝细胞癌（HCC）因其高死亡率和对标准治疗的耐药性，仍然是一个重大的全球健康问题。索拉非尼是不可切除HCC的一线全身治疗药物，但由于耐药性和严重副作用，其疗效有限。最近的研究表明，将索拉非尼与免疫疗法，特别是自然杀伤（NK）细胞联合使用，可能会改善治疗效果。本研究在大鼠HCC模型中检测了索拉非尼与经白细胞介素-12（IL-12）和白细胞介素-18（IL-18）预处理的NK细胞联合使用的有效性。使用磁共振成像（MRI）和组织学分析评估肿瘤进展和治疗效果。结果表明，联合治疗显著降低了肿瘤生长，增加了肿瘤细胞密度，并抑制了肿瘤微环境中的血管生成和纤维化。经索拉非尼和IL-12/IL-18预处理的NK细胞联合使用，通过克服耐药性和调节免疫反应增强了肿瘤抑制作用。本研究表明，这种联合治疗可能是一种有前景的HCC治疗策略，既能提供直接的抗肿瘤作用，又能改变肿瘤微环境以获得更好的临床结果。
