IL-25 blockade inhibits metastasis in breast cancer
Authors:
Open Access
- 1 December 2016
- journal article
- research article
- Published by Oxford University Press (OUP) in Protein & Cell
- Vol. 8 (3) , 191-201
Abstract
Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4+ T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.Keywords
This publication has 52 references indexed in Scilit:
- Inhibition of colitis by IL-25 associates with induction of alternatively activated macrophagesInflammatory Bowel Diseases, 2012
- Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammationJournal of Experimental Medicine, 2011
- Innate signals from Nod2 block respiratory tolerance and program TH2-driven allergic inflammationJournal of Allergy and Clinical Immunology, 2010
- Regulation of IL-9 expression by IL-25 signalingNature Immunology, 2010
- CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of MacrophagesCancer Cell, 2009
- Cancer-related inflammationNature, 2008
- IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC–activated Th2 memory cellsJournal of Experimental Medicine, 2007
- Interleukin 25 promotes the initiation of proallergic type 2 responsesJournal of Experimental Medicine, 2007
- Dissemination and growth of cancer cells in metastatic sitesNature Reviews Cancer, 2002
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProceedings of the National Academy of Sciences, 2001