Endogenous IL-12 triggers an antiangiogenic program in melanoma cells

Irma Airoldi, Emma Di Carlo, Claudia Cocco, Giuseppe Taverniti, Tommaso D'Antuono, Emanuela Ognio, Morihiro Watanabe, Domenico Ribatti, Vito Pistoia

Research output: Contribution to journalArticle

Abstract

The IL12RB2 gene acts as a tumor suppressor in human B cell malignancies. Indeed, Il12rb2 knockout (KO) mice develop spontaneously B cell tumors, but also lung epithelial tumors. This latter phenotype may be related to (i) impairment of host IL-12-mediated immunosurveillance and/or (ii) IL-12 inability to inhibit directly the growth of IL-12 unresponsive malignant cells. To address this issue, we transplanted IL-12R+ B16 melanoma cells into syngeneic Il12rb2 KO mice with the following rationale: (i) these mice have severe defects in IFN-γ production, as well as in cytotoxic T lymphocyte and natural killer cell cytotoxicity, and (ii) they produce but do not use IL-12 that can potentially bind to and target tumor cells only. Il12rb2 KO mice displayed higher endogenous serum levels of IL-12 and developed smaller B16 tumors than WT animals. These tumors showed reduced proliferation, increased apoptosis, and defective microvessel formation related to down-regulated expression of a set of proangiogenic genes previously unrelated to IL-12. Such effects depended on direct activity of endogenous IL-12 on tumor cells in KO mice, and hydrodynamic delivered IL-12 caused further reduced tumorigenicity of B16 cells in these mice. A previously undescribed mechanism of the IL-12 antitumor activity has been here identified and characterized.

Original languageEnglish
Pages (from-to)3996-4001
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number10
DOIs
Publication statusPublished - Mar 6 2007

Keywords

  • Angiogenesis
  • Cytokines
  • Tumor immunology

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    Airoldi, I., Di Carlo, E., Cocco, C., Taverniti, G., D'Antuono, T., Ognio, E., Watanabe, M., Ribatti, D., & Pistoia, V. (2007). Endogenous IL-12 triggers an antiangiogenic program in melanoma cells. Proceedings of the National Academy of Sciences of the United States of America, 104(10), 3996-4001. https://doi.org/10.1073/pnas.0609028104