ACCUMULATION OF IL-12-ACTIVATED ANTITUMOR EFFECTOR-CELLS INTO LYMPH-NODES OF TUMOR-BEARING MICE

aSimultaneous administration of high dose of IL-12 into tumor-inoculat ed mice resulted in a marked reduction of tumor growth in parallel wit h the augmented generation of cytotoxic T-cells, natural killer (NK) c ells and IFN-gamma-producing Th cells. We found that these IL-12-activ ated antitumor effector cells preferentially accumulated in peripheral lymph nodes concomitantly with lymphadenopathy. However, IL-12 rather induced disappearance of antitumor effector cells including CD4(+) T, CD8(+) T and NK cells from spleen in spite of inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16FO-bearing mice showed a marked IFN-gamma production in response to not only IL-2, IL-12, an ti CD3 mAb but also B16FO melanoma cells. Moreover, they could lyse B1 6FO melanoma cells in a long-term cytotoxicity assay. It was also conf irmed that IL-12-activated IFN-gamma producing Th1 cells were accumula ted in tumor local site. Thus, IL-12 appeared to have a capability of stimulating selective migration of antitumor cells into lymph nodes an d tumor local sites. (C) 1998 Elsevier Science B.V. All rights reserve d.