title: Cutaneous tumors cease CXCL9/Mig production as a result of IFN-γ-mediated immunoediting.
abstract: During growth in the host, tumor cells are subjected to the stresses of innate and adaptive immunity (immunoediting), which provoke epigenetic changes in the tumor and increase tumor resistance to these immune responses. Our recent studies in methylcholanthrene-induced fibrosarcomas have indicated the appearance and rapid growth of tumor variants deficient in producing the T cell chemoattractant chemokine CXCL9/Mig, an important component of antitumor immunity. In the current report, we demonstrate that highly tumorigenic Mig-deficient tumor variants arise in both cutaneous fibrosarcoma and melanoma as a result of immune stress imposed by IFN-γ and T cells. The consequence of the loss of tumor-derived Mig expression is the increased resistance of Mig-deficient tumors to T cell-mediated immunity, which promotes the accelerated growth of these tumor variants. Remarkably, the ability of Mig-deficient tumor cells to express another CXCR3 ligand, CXCL10/IFN-γ-inducible protein, does not compensate for the absent antitumor functions of Mig, suggesting a nonredundant role for this chemokine in the suppression of tumor growth. To our knowledge, these studies report for the first time that IFN-γ-mediated stress leads to the loss of specific chemokine expression by tumor cells, which in turn promotes tumor growth and evasion of the immune response.
authors.affiliation: Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Marianne
authors.initials: M
authors.lastname: Petro
authors.forename: Danielle
authors.initials: D
authors.lastname: Kish
authors.forename: Olga A
authors.initials: OA
authors.lastname: Guryanova
authors.forename: Galina
authors.initials: G
authors.lastname: Ilyinskaya
authors.forename: Anna
authors.initials: A
authors.lastname: Kondratova
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fairchild
authors.forename: Anton V
authors.initials: AV
authors.lastname: Gorbachev
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology*
chemical_list: D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D007371:Interferon-gamma