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

Ahmed Lasfar, Andrew de la Torre, Walid Abushahba, Karine A. Cohen-Solal, Ismael Castaneda, Yao Yuan, Kenneth Reuhl, Andrew Zloza, Elizabeth Raveche, Debra L. Laskin, Sergei V. Kotenko

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)49259-49267
Number of pages9
JournalOncotarget
Volume7
Issue number31
DOIs
StatePublished - 2016

All Science Journal Classification (ASJC) codes

  • Oncology

Keywords

  • HCV
  • Hepatocellular carcinoma
  • IFN therapy
  • IFN-α/IFN-γ combination
  • Tumor immunity

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    Lasfar, A., de la Torre, A., Abushahba, W., Cohen-Solal, K. A., Castaneda, I., Yuan, Y., Reuhl, K., Zloza, A., Raveche, E., Laskin, D. L., & Kotenko, S. V. (2016). Concerted action of IFN-α and IFN-γ induces local NK cell immunity and halts cancer growth. Oncotarget, 7(31), 49259-49267. https://doi.org/10.18632/oncotarget.10272