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
✍ Scribed by Giovana R. Thomas; Zhong Chen; Ileana Enamorado; Caren Bancroft; Carter Van Waes
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- French
- Weight
- 313 KB
- Volume
- 86
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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-␥. 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 B7E11-4scid. 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 B7E11-4scid in congenic BALB/c IFN-␥ knockout mice, indicating that expression of the CD80 costimulatory molecule and IFN-␥ 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-␥ by the host promote IL-12 induced regression of SCC. Int.