title: Decreased accumulation of immune regulatory cells is correlated to the antitumor effect of IFN-γ overexpression in the tumor.
abstract: During mammary tumorigenesis, there is a profound tumor-induced immunosuppression and a progressive thymic atrophy associated with tumor development. IFN-γ has been shown to be effective in enhancing antitumor responses in several tumor models, however, how IFN-γ exerts its anti-tumor effect is largely controversial. In the present study we have used a mammary tumor model to investigate whether the levels of IFN-γ have an important role in the tumor-induced immuno-suppression as well as in the pathogenesis of the thymic atrophy. We evaluated this possibility using DA-3 cells transfected to express IFN-γ (DA-3/IFN-γ), a system that provides constant, local production of IFN-γ within the tumor microenvironment. Overexpression of IFN-γ in the mammary tumor results in a marked delay of tumor growth, a reduction in regulatory T cells and myeloid-derived suppressor cells accumulation mostly due to down-regulation of chemokines implicated in the recruitment of immune regulatory cells, and a blockage in the tumor-associated thymus atrophy. Collectively, our data suggest that the replacement of the faulty levels of IFN-γ in the tumor results in a diminution of the tumor-induced immune suppression caused by the mammary tumor development.
authors.affiliation: Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carrio
authors.forename: Marta
authors.initials: M
authors.lastname: Torroella-Kouri
authors.forename: Stephania
authors.initials: S
authors.lastname: Libreros
authors.forename: Ramón A
authors.initials: RA
authors.lastname: García-Areas
authors.forename: Vijaya
authors.initials: V
authors.lastname: Iragavarapu-Charyulu
authors.forename: Diana M
authors.initials: DM
authors.lastname: López
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014162:Transfection; D059016:Tumor Microenvironment / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018925:Chemokines; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma