IL-12- and IL-2-induced tumor regression in a new murine model of oral squamous-cell carcinoma is promoted by expression of the CD80 co-stimulatory molecule and interferon-γ

Giovana R. Thomas, Zhong Chen, Ileana Enamorado, Caren Bancroft, Carter Van Waes

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Therapy with IL-12 or IL-2 induces tumor regression in only a few patients with head-and-neck squamous cell carcinoma (SCC), and the factors promoting responsiveness have not been well defined. In this study, we examined whether combined IL-12 and IL-2 therapy can induce tumor regression in a new murine model of oral SCC and determined if the anti-tumor response is promoted by expression of the immune co-stimulatory molecule CD80 and cytokine IFN-γ. In CD80-positive or -negative subclones of a BALB/c oral SCC line in syngeneic mice, we showed that systemic rIL-12 alone was comparable in effectiveness to combined therapy with IL- 12 and peri-tumoral rIL-2, inducing complete regression of the CD80+ line B7EII-4scid. However, therapy with these cytokines had no effect on growth of the CD80- subclone B7E3- 4scid and did not induce complete regression of the CD80+ subclone B7EII- 4scid in congenic BALB/c IFN-γ knockout mice, indicating that expression of the CD80 costimulatory molecule and IFN-γ contributes to tumor regression. In cytokine-treated mice that rejected the CD80+ SCC line, an increase in infiltrating CD4+ lymphocytes and apoptotic bodies within the tumor specimens was observed, and resistance to rechallenge with the same tumor was detected in 50% of recipients, consistent with an immune response. Our results provide evidence that regression of oral head-and-neck SCC may be induced by therapy with systemic IL-12 and that expression of the CD80 co- stimulatory molecule by SCC and IFN-γ by the host promote IL-12 induced regression of SCC.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalInternational Journal of Cancer
Volume89
Issue number2
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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