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Genome-wide analysis of molecular changes in IL-12-induced control of mammary carcinoma via IFN-gamma-independent mechanisms.

TitleGenome-wide analysis of molecular changes in IL-12-induced control of mammary carcinoma via IFN-gamma-independent mechanisms.
Publication TypeJournal Article
Year of Publication2004
AuthorsShi X, Cao S, Mitsuhashi M, Xiang Z, Ma X
JournalJ Immunol
Volume172
Issue7
Pagination4111-22
Date Published2004 Apr 01
ISSN0022-1767
KeywordsAnimals, Antineoplastic Agents, Cell Line, Tumor, Chemokines, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Growth Inhibitors, Interferon-gamma, Interleukin-12, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Mice, Knockout, Neoplasm Transplantation, Neovascularization, Pathologic, Oligonucleotide Array Sequence Analysis, Recombinant Proteins
Abstract

IL-12 is a major activator of tumor-killing NK cells and CTL. IFN-gamma mediates most of the well-known immunological activities of IL-12. In this study, we report IFN-gamma-independent activities induced by therapeutic application of rIL-12 in restricting tumor growth and metastasis in the 4T1 murine mammary carcinoma model. IFN-gamma-deficient mice carrying 4T1 tumor exhibit no gross defect in the number of tumor-infiltrating lymphocytes but have exaggerated angiogenesis in the tumor. Administration of IL-12 is able to constrict blood vessels in the tumor in the absence of IFN-gamma, and retains certain therapeutic efficacy even when applied late during tumor progression. IL-12 exposure in vivo does not irreversibly alter the immunogenicity of the tumor. Finally, global gene expression analysis of primary tumors reveals IL-12-induced molecular patterns and changes, implicating a number of novel genes potentially important for IFN-gamma-independent immune responses against the tumor, for IL-12-mediated antiproliferation, antimetastasis, and antiangiogenesis activities.

DOI10.4049/jimmunol.172.7.4111
Alternate JournalJ Immunol
PubMed ID15034023
PubMed Central IDPMC2956987
Grant ListR01 CA100223 / CA / NCI NIH HHS / United States
R01 CA100223-01A1 / CA / NCI NIH HHS / United States
CA79772 / CA / NCI NIH HHS / United States

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