Regulation of Carcinogenesis by IL-5 and CCL11: A Potential Role for Eosinophils in Tumor Immune Surveillance

• Published in: Journal of Immunology 2007-04, Vol.178 (7), p.4222-4229
• Main Authors: Simson, Ljubov, Ellyard, Julia I, Dent, Lindsay A, Matthaei, Klaus I, Rothenberg, Marc E, Foster, Paul S, Smyth, Mark J, Parish, Christopher R
• Format: Article
• Language: English
• Subjects: Animals; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Chemokine CCL11; Chemokines, CC - genetics; Chemokines, CC - physiology; Eosinophils - immunology; Fibrosarcoma - chemically induced; Fibrosarcoma - genetics; Fibrosarcoma - immunology; Immunologic Surveillance - genetics; Interleukin-5 - genetics; Interleukin-5 - metabolism; Interleukin-5 - physiology; Male; Methylcholanthrene - toxicity; Mice; Mice, Transgenic; Neoplasms - chemically induced; Neoplasms - genetics; Neoplasms - immunology
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.7.4222

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.