title: 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.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Gillgrass
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Navkiran
authors.initials: N
authors.lastname: Gill
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Artem
authors.initials: A
authors.lastname: Babian
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada ashkara@mcmaster.ca.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D019409:Interleukin-15 / Q000008:administration & dosage / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental; D008546:Melanoma, Experimental; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis
chemical_list: D019409:Interleukin-15