A role of interferon-gamma (IFN-gamma) in tumor immunity: T cells with thecapacity to reject tumor cells are generated but fail to migrate to tumor sites in IFN-gamma-deficient mice

IFN-gamma -deficient (IFN-gamma (-/-)) mice induce potent in vitro immune r esponses such as anti-allo mixed lymphocyte reaction and CTL responses, whe reas they often fail to exhibit in vivo immunity. Here, we investigated whe ther there exists a defect in tumor rejection responses and if so, which pr ocess of responses is impaired. IFN-gamma (-/-) and wild-type (WT) BALB/c m ice were immunized with attenuated syngeneic CSA1M tumor cells. The capacit y of T cells to mediate tumor protection was examined in Winn assays to ass ess the growth of tumor cells admired with tumor-sensitized T cells. Spleni c T cells from both groups of mice exhibited comparable levels of tumor-neu tralizing activity. When portions of immunized mice were directly challenge d with viable tumor cells, tumor rejection was induced only in WT mice. CD4 (+) and CD8(+) T-cell infiltration were observed at the site of tumor chall enge in WT mice, whereas such a T-cell infiltration did not occur in IFN-ga mma (-/-) mice, Similarly, splenic T cells from interleukin 12-treated CSA1 M-bearing IFN-gamma (-/-) and WT mice neutralized tumor cells at comparable efficacies in Winn assays. However, the migration of these T cells to tumo r masses and the resultant interleukin 12-induced tumor regression took pla ce in WT mice, but neither intratumoral T-cell infiltration nor tumor regre ssion occurred in IFN-gamma (-/-) mice, These results indicate a critical r equirement for IFN-gamma in the process of inducing T-cell migration to tum or sites rather than of generating antitumor protective T cells.