ENHANCED INDUCTION OF VERY LATE ANTIGEN 4 LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN 1-DEPENDENT T-CELL MIGRATION TO TUMOR SITES FOLLOWING ADMINISTRATION OF INTERLEUKIN-12/

Administration of interleukin 12 (IL-12) into mice bearing CSA1M, OV-H M, Meth A, or MCH-1-A1 tumor induced complete regression of CSA1M and OV-HM tumors but induced only a slight growth inhibition of Meth A and MCH-1-A1 tumors, These effects of IL-12 were associated with high and only marginal levels of T-cell infiltration into CSA1M/OV-HM and Meth A/MCH-1-A1 tumor masses, respectively, Here, we investigated the role of IL-12 in the induction of T-cell migration. Spleen cells from untr eated or IL-12-treated CSA1M-bearing mice were stained in vitro with a fluorescein chemical and transferred i.v. into IL-12-untreated CSA1M- bearing mice. Migration of donor cells was quantitated by counting the number of fluorescent cells on cryostat sections of tumor masses. Alt hough only a slight migration was detected for spleen cells from IL-12 -untreated CSA1M-bearing as well as IL-12-treated or untreated normal mice, enhanced migration was observed for cells from IL-12-treated CSA 1M-bearing mice, A similar enhanced migration was observed for the OV- HM model. In contrast, such an enhancement was only marginal in the Me th A and MCH-1-A1 models, Immunohistochemical studies of tumors from I L-12-treated mice revealed that the predominant T-cell subset was CD4( +) in CSA1M and CD8(+) in OV-HM tumor masses. Consistent with this obs ervation, the dominant subset of migrating T cells was found to be CD4 (+) in the CSA1M and CD8(+) in the OV-HM models, T-cell migration was inhibited by pretreatment of recipients with either combination of ant i-very late antigen 4 + anti-vascular cell adhesion molecule 1 or anti -lymphocyte function-associated antigen 1 + anti-intercellular adhesio n molecule 1 monoclonal antibody, These results indicate that IL-12 ca n confer T cells with a capacity to migrate to tumor sites through ver y late antigen 4/lymphocyte function-associated antigen 1 adhesion pat hways and that the in vivo acquisition of such a capacity following IL -12 treatment correlates with the induction of tumor regression.