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The absence or overexpression of IL-15 drastically alters breast cancer metastasis via effects on NK cells, CD4 T cells, and macrophages.

Abstract
IL-15 is a cytokine that can affect many immune cells, including NK cells and CD8 T cells. In several tumor models, IL-15 delays primary tumor formation and can prevent or reduce metastasis. In this study, we have employed a model of breast cancer metastasis to examine the mechanism by which IL-15 affects metastasis. When breast tumor cells were injected i.v. into IL-15(-/-), C57BL/6, IL-15 transgenic (TG) and IL-15/IL-15Rα-treated C57BL/6 mice, there were high levels of metastasis in IL-15(-/-) mice and virtually no metastasis in IL-15 TG or IL-15-treated mice. In fact, IL-15(-/-) mice were 10 times more susceptible to metastasis, whereas IL-15 TG mice were at least 10 times more resistant to metastasis when compared with control C57BL/6 mice. Depletion of NK cells from IL-15 TG mice revealed that these cells were important for protection from metastasis. When NK cells were depleted from control C57BL/6 mice, these mice did not form as many metastatic foci as IL-15(-/-) mice, suggesting that other cell types may be contributing to metastasis in the absence of IL-15. We then examined the role of CD4 T cells and macrophages. In IL-15(-/-) mice, in vivo depletion of CD4 T cells decreased metastasis. The lack of IL-15 in IL-15(-/-) mice, and possibly the Th2-polarized CD4 T cells, was found to promote the formation of M2 macrophages that are thought to contribute to metastasis formation. This study reveals that whereas IL-15 effects on NK cells are important, it also has effects on other immune cells that contribute to metastasis.
AuthorsAmy Gillgrass, Navkiran Gill, Artem Babian, Ali A Ashkar
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 12 Pg. 6184-91 (Dec 15 2014) ISSN: 1550-6606 [Electronic] United States
PMID25355926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 by The American Association of Immunologists, Inc.
Chemical References
  • Interleukin-15
Topics
  • Animals
  • Breast Neoplasms (genetics, immunology, pathology)
  • CD4-Positive T-Lymphocytes (immunology, metabolism)
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Interleukin-15 (administration & dosage, genetics)
  • Killer Cells, Natural (immunology, metabolism)
  • Lung Neoplasms (genetics, pathology, secondary)
  • Macrophages (immunology, metabolism)
  • Mammary Neoplasms, Experimental
  • Melanoma, Experimental
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Metastasis

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