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

Abstract

// Ahmed Lasfar 1, 2 , Andrew de la Torre 3, 4 , Walid Abushahba 5 , Karine A. Cohen-Solal 2, 6 , Ismael Castaneda 3 , Yao Yuan 7 , Kenneth Reuhl 1, 2 , Andrew Zloza 2, 6 , Elizabeth Raveche 2, 7 , Debra L. Laskin 1, 2 , Sergei V. Kotenko 5 1 Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA 2 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA 3 Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA 4 St Joseph’s Medical Center, Paterson, NJ, USA 5 Department 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 6 Section of Surgical Oncology Research, Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA 7 Department of Pathology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA Correspondence to: Ahmed Lasfar, email: ahmed.lasfar@pharmacy.rutgers.edu , lasfarah@gmail.com 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 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-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.