Regulation of carcinogenesis by IL-5 and CCL11: a potential role for eosinophils in tumor immune surveillance.
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.
Simson
Ljubov
L
Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Mills Road Acton, Canberra, Australian Capital Territory, Australia.
Ellyard
Julia I
JI
Dent
Lindsay A
LA
Matthaei
Klaus I
KI
Rothenberg
Marc E
ME
Foster
Paul S
PS
Smyth
Mark J
MJ
Parish
Christopher R
CR
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D004804:Eosinophils / Q000276:immunology*; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D007157:Immunologic Surveillance / Q000235:genetics*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D008748:Methylcholanthrene