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-gamma

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 whet her combined IL-12 and IL-2 therapy can induce tumor regression in a new mu rine model of oral SCC and determined if the anti-tumor response is promote d by expression of the immune co-stimulatory molecule CD80 and cytokine IFN -gamma, In CD80-positive or -negative subclones of a BALB/c oral SCC line i n syngeneic mice, we showed that systemic rIL-12 alone was comparable in ef fectiveness to combined therapy with IL-12 and peri-tumoral rIL-2, inducing complete regression of the CD80(+) line B7E1 1-4scid. However, therapy wit h these cytokines had no effect on growth of the CD80(-) subclone B7E3-4sci d and did not induce complete regression of the CD80(+) subclone B7E1 1-4sc id in congenic BALB/c IFN-gamma knockout mice, indicating that expression o f the CD80 co stimulatory molecule and IFN-gamma contributes to tumor regre ssion, In cytokine-treated mice that rejected the CD80(+) SCC line, an incr ease in infiltrating CD4(+) lymphocytes and apoptotic bodies within the tum or specimens was observed, and resistance to rechallenge with the same tumo r was detected in 50% of recipients, consistent with an immune response, Ou r 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-gamma by the host promote IL-12 induced regression of SCC. Published 2000 Wiley-Liss, Inc(dagger).