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https://hdl.handle.net/2440/43405
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Type: | Journal article |
Title: | Regulation of carcinogenesis by IL-5 and CCL11: A potential role for eosinophils in tumor immune surveillance |
Author: | Simson, L. Ellyard, J. Dent, L. Matthaei, K. Rothenberg, M. Foster, P. Smyth, M. Parish, C. |
Citation: | Journal of Immunology, 2007; 178(7):4222-4229 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2007 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Ljubov Simson, Julia I. Ellyard, Lindsay A. Dent, Klaus I. Matthaei, Marc E. Rothenberg, Paul S. Foster, Mark J. Smyth and Christopher R. Parish |
Abstract: | The role of the immune system in the surveillance of transformed cells has seen a resurgence of interest in the last 10 years, with a substantial body of data in mice and humans supporting a role for the immune system in host protection from tumor development and in shaping tumor immunogenicity. A number of earlier studies have demonstrated that eosinophils, when recruited into tumors, can very effectively eradicate transplantable tumors. In this study, we investigated whether eosinophils also play a role in tumor immune surveillance by determining the incidence of methylcholanthrene (MCA)-induced fibrosarcomas in IL-5 transgenic mice that have greatly enhanced levels of circulating eosinophils, CCL11 (eotaxin-1)-deficient mice that lack a key chemokine that recruits eosinophils into tissues, and the eosinophil-deficient mouse strains, IL-5/CCL11(-/-) and DeltadblGATA. It was found that MCA-induced tumor incidence and growth were significantly attenuated in IL-5 transgenic mice of both the BALB/c and C57BL/6 backgrounds. Histological examination revealed that the protective effect of IL-5 was associated with massively enhanced numbers of eosinophils within and surrounding tumors. Conversely, there was a higher tumor incidence in CCL11(-/-) BALB/c mice, which was associated with a reduced eosinophil influx into tumors. This correlation was confirmed in the eosinophil-deficient IL-5/CCL11(-/-) and DeltadblGATA mouse strains, where tumor incidence was greatly increased in the total absence of eosinophils. In addition, subsequent in vitro studies found that eosinophils could directly kill MCA-induced fibrosarcoma cells. Collectively, our data support a potential role for the eosinophil as an effector cell in tumor immune surveillance. |
Keywords: | Eosinophils Animals Mice, Transgenic Mice Neoplasms Fibrosarcoma Cell Transformation, Neoplastic Methylcholanthrene Chemokines, CC Interleukin-5 Immunologic Surveillance Male Chemokine CCL11 |
Description: | Copyright © 2007 by The American Association of Immunologists, Inc. |
DOI: | 10.4049/jimmunol.178.7.4222 |
Published version: | http://www.jimmunol.org/cgi/content/abstract/178/7/4222 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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