ORIGINAL ARTICLE

Cancer Immunology, Immunotherapy

, Volume 48, Issue 2, pp 63-70

Interferon γ and antisense transforming growth factor β transgenes synergize to enhance the immunogenicity of a murine mammary carcinoma

  • Julie A. McEarchernAffiliated withDepartment of Microbiology and Immunology, University of Arizona, 1501 N. Campbell, Tucson, AZ 85724, USA Fax: +1-520-626-2100
  • , David G. BesselsenAffiliated withDepartment of Veterinary Sciences and Microbiology and University Animal Care University of Arizona, Tucson, AZ 85724, USA
  • , Emmanuel T. AkporiayeAffiliated withDepartment of Microbiology and Immunology, University of Arizona, 1501 N. Campbell, Tucson, AZ 85724, USA Fax: +1-520-626-2100

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Abstract

Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that contributes to the immunological escape of tumor cells. In a previous study we demonstrated that inhibition of TGFβ production by EMT6 murine mammary tumor cells expressing an antisense TGF-β transgene reduces their tumorigenicity. On the basis of this observation we hypothesized that down-regulation of TGFβ production coupled with interferon γ (IFNγ) stimulation would induce an immune response superior to that generated by either strategy alone. In this study, EMT6 tumor cells expressing antisense TGFβ were transduced with the murine IFNγ gene. Tumor cells expressing either or both transgenes grew more slowly than mock-transduced tumors. Dual-transgene-expressing tumor cells were more immunogenic than tumor cells expressing either transgene alone. Studies in mice depleted of T cell subsets indicated that CD8+ T cells are the primary effectors of the antitumor activity observed. These results suggest that down-regulation of immunosuppression combined with cytokine-mediated immune augmentation is a useful strategy to improve antitumor immunity.

Key words Antisense TGFβ IFNγ Mammary carcinoma Immunosuppression Immunogenicity