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* Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia;
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia;
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia;
Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 46229; and
¶ Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
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 
dblGATA. 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 dblGATA 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Program Grants to C.R.P. (209618), M.J.S. (251608), P.S.F. and K.I.M. (224207), a Project Grant to L.A.D. (157964) from the National Health and Medical Research Council of Australia, and a Peter Doherty Biomedical Fellowship (National Health and Medical Research Council) to L.S.
2 Address correspondence and reprint requests to Dr. Christopher R. Parish, John Curtin School of Medical Research, Division of Immunology and Genetics, Mills Road Acton, Canberra, Australian Capital Territory, Australia. E-mail address: Christopher.Parish{at}anu.edu.au
3 Abbreviations used in this paper: Tg, transgenic; MCA, methylcholanthrene; WT, wild type; HPF, high-powered field.
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