Lasfar Ahmed, de laTorre Andrew, Abushahba Walid, Cohen-Solal Karine A, Castaneda Ismael, Yuan Yao, Reuhl Kenneth, Zloza Andrew, Raveche Elizabeth, Laskin Debra L, Kotenko Sergei V
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Oncotarget. 2016 Aug 2;7(31):49259-49267. doi: 10.18632/oncotarget.10272.
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. No significant improvement has been reported with currently available systemic therapies. IFN-α has been tested in both clinic and animal models and only moderate benefits have been observed. In animal models, similar modest antitumor efficacy has also been reported for IFN-λ, a new type of IFN that acts through its own receptor complex. In the present study, the antitumor efficacy of the combination of IFN-α and IFN-λ was tested in the BNL mouse hepatoma model. This study was accomplished by using either engineered tumor cells (IFN-α/IFN-λ gene therapy) or by directly injecting tumor-bearing mice with IFN-α/IFN-λ. Both approaches demonstrated that IFN-α/IFN-λ combination therapy was more efficacious than IFN monotherapy based on either IFN-α or IFN-λ. In complement to tumor surgery, IFN-α/IFN-λ combination induced complete tumor remission. Highest antitumor efficacy has been obtained following local administration of IFN-α/IFN-λ combination at the tumor site that was associated with strong NK cells tumor infiltration. This supports the use of IFN-α/IFN-λ combination as a new cancer immunotherapy for stimulating antitumor response after cancer surgery.
肝细胞癌（HCC）是最常见的肝癌类型。目前可用的全身治疗方法尚未有显著改善。干扰素-α（IFN-α）已在临床和动物模型中进行了测试，仅观察到中等程度的益处。在动物模型中，对于通过自身受体复合物发挥作用的新型干扰素IFN-λ，也报道了类似的适度抗肿瘤疗效。在本研究中，在BNL小鼠肝癌模型中测试了IFN-α与IFN-λ联合使用的抗肿瘤疗效。该研究通过使用工程化肿瘤细胞（IFN-α/IFN-λ基因治疗）或直接向荷瘤小鼠注射IFN-α/IFN-λ来完成。两种方法均表明，基于IFN-α或IFN-λ，IFN-α/IFN-λ联合治疗比单一干扰素治疗更有效。作为肿瘤手术的补充，IFN-α/IFN-λ联合治疗可诱导肿瘤完全缓解。在肿瘤部位局部给予IFN-α/IFN-λ联合治疗后获得了最高的抗肿瘤疗效，这与自然杀伤细胞（NK细胞）大量浸润肿瘤有关。这支持将IFN-α/IFN-λ联合治疗作为一种新的癌症免疫疗法，用于在癌症手术后刺激抗肿瘤反应。
