Concerted action of IFN-α and IFN-γ induces local NK cell immunity and halts cancer growth

Abstract

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-γ, 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-γ was tested in the BNL mouse hepatoma model. This study was accomplished by using either engineered tumor cells (IFN-α/IFN-γ gene therapy) or by directly injecting tumor-bearing mice with IFN-α/IFN-γ. Both approaches demonstrated that IFN-α/ IFN-γ combination therapy was more efficacious than IFN monotherapy based on either IFN-α or IFN-γ. In complement to tumor surgery, IFN-α/IFN-γ combination induced complete tumor remission. Highest antitumor efficacy has been obtained following local administration of IFN-α/IFN-γ combination at the tumor site that was associated with strong NK cells tumor infiltration. This supports the use of IFN-α/IFN-γ combination as a new cancer immunotherapy for stimulating antitumor response after cancer surgery.