Concerted action of IFN-α and IFN-λ induces local NK cell immunity and halts cancer growth
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Ahmed Lasfar1,2, Andrew de la Torre3,4, Walid Abushahba5, Karine A. Cohen-Solal2,6, Ismael Castaneda3, Yao Yuan7, Kenneth Reuhl1,2, Andrew Zloza2,6, Elizabeth Raveche2,7, Debra L. Laskin1,2, Sergei V. Kotenko5
1Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA
2Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
3Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA
4St Joseph’s Medical Center, Paterson, NJ, USA
5Department of Microbiology, Biochemistry and Molecular Genetics, Center for Immunity and Inflammation, University Hospital Cancer Center, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ, USA
6Section of Surgical Oncology Research, Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
7Department of Pathology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA
Keywords: hepatocellular carcinoma, HCV, IFN therapy, IFN-α/IFN-λ combination, tumor immunity
Received: April 05, 2016 Accepted: May 16, 2016 Published: June 24, 2016
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.
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