title: Concerted action of IFN-α and IFN-λ 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-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.
authors.affiliation: 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.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Lasfar
authors.affiliation: Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.|St Joseph's Medical Center, Paterson, NJ, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: de laTorre
authors.affiliation: 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.
authors.forename: Walid
authors.initials: W
authors.lastname: Abushahba
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|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.
authors.forename: Karine A
authors.initials: KA
authors.lastname: Cohen-Solal
authors.affiliation: Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Ismael
authors.initials: I
authors.lastname: Castaneda
authors.affiliation: Department of Pathology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Reuhl
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.|Department of Pathology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Raveche
authors.affiliation: 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.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
authors.affiliation: 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.
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Kotenko
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D007167:Immunotherapy; D016898:Interferon-alpha / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D016898:Interferon-alpha; D007371:Interferon-gamma
keywords: HCV; IFN therapy; IFN-α/IFN-λ combination; hepatocellular carcinoma; tumor immunity