Interleukin-12 (IL-12) has potent antitumor activities via natural killer cells and cytotoxic T lymphocytes. However, the molecular mechanisms whereby IL-12 induces tumoricidal activities are poorly understood. Here, we report the genome-wide analysis of gene expression in a primary murine mammary carcinoma model that resembles human breast cancer, following the therapeutic application of recombinant IL-12, which restricted tumor growth and metastasis. IL-12 was able to curtail neovascularization in the tumor as well as enhance the number of tumor-infiltrating lymphocytes. Comprehensive examination of global gene expression revealed IL-12-induced molecular changes associated with tumor regression and reduced lung metastasis, thus providing a high-resolution snapshot of a host response against a developing malignancy and a rich source of potential targets for therapeutic intervention of breast cancer.
Copyright 2004 Wiley-Liss, Inc.