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 Laskin, Sergei Kotenko

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 - Jan 1 2016

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Natural Killer Cells
Immunity
Growth
Neoplasms
Hepatocellular Carcinoma
Animal Models
Liver Neoplasms
Genetic Therapy
Immunotherapy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology

Keywords

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

Cite this

Lasfar, Ahmed ; de la Torre, Andrew ; Abushahba, Walid ; Cohen-Solal, Karine A. ; Castaneda, Ismael ; Yuan, Yao ; Reuhl, Kenneth ; Zloza, Andrew ; Raveche, Elizabeth ; Laskin, Debra ; Kotenko, Sergei. / Concerted action of IFN-α and IFN-γ induces local NK cell immunity and halts cancer growth. In: Oncotarget. 2016 ; Vol. 7, No. 31. pp. 49259-49267.
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Lasfar, A, de la Torre, A, Abushahba, W, Cohen-Solal, KA, Castaneda, I, Yuan, Y, Reuhl, K, Zloza, A, Raveche, E, Laskin, D & Kotenko, S 2016, 'Concerted action of IFN-α and IFN-γ induces local NK cell immunity and halts cancer growth', Oncotarget, vol. 7, no. 31, pp. 49259-49267. https://doi.org/10.18632/oncotarget.10272

Concerted action of IFN-α and IFN-γ induces local NK cell immunity and halts cancer growth. / Lasfar, Ahmed; de la Torre, Andrew; Abushahba, Walid; Cohen-Solal, Karine A.; Castaneda, Ismael; Yuan, Yao; Reuhl, Kenneth; Zloza, Andrew; Raveche, Elizabeth; Laskin, Debra; Kotenko, Sergei.

In: Oncotarget, Vol. 7, No. 31, 01.01.2016, p. 49259-49267.

Research output: Contribution to journalArticle

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AU - Lasfar, Ahmed

AU - de la Torre, Andrew

AU - Abushahba, Walid

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AU - Castaneda, Ismael

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AU - Reuhl, Kenneth

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AU - Raveche, Elizabeth

AU - Laskin, Debra

AU - Kotenko, Sergei

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Lasfar A, de la Torre A, Abushahba W, Cohen-Solal KA, Castaneda I, Yuan Y et al. Concerted action of IFN-α and IFN-γ induces local NK cell immunity and halts cancer growth. Oncotarget. 2016 Jan 1;7(31):49259-49267. https://doi.org/10.18632/oncotarget.10272