title: Cutting edge: systemic inhibition of angiogenesis underlies resistance to tumors during acute toxoplasmosis.
abstract: The ability of various infections to suppress neoplastic growth has been well documented. This phenomenon has been traditionally attributed to infection-induced concomitant, cell-mediated antitumor immunity. We found that infection with Toxoplasma gondii effectively blocked neoplastic growth of a nonimmunogenic B16.F10 melanoma. Moreover, this effect was independent of cytotoxic T or NK cells, production of NO by macrophages, or the function of the cytokines IL-12 and TNF-alpha. These findings suggested that antitumor cytotoxicity was not the primary mechanism of resistance. However, infection was accompanied by strong, systemic suppression of angiogenesis, both in a model system and inside the nascent tumor. This suppression resulted in severe hypoxia and avascular necrosis that are incompatible with progressive neoplastic growth. Our results identify the suppression of tumor neovascularization as a novel mechanism critical for infection-induced resistance to tumors.
authors.affiliation: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hunter
authors.forename: D
authors.initials: D
authors.lastname: Yu
authors.forename: M
authors.initials: M
authors.lastname: Gee
authors.forename: C V
authors.initials: CV
authors.lastname: Ngo
authors.forename: C
authors.initials: C
authors.lastname: Sevignani
authors.forename: M
authors.initials: M
authors.lastname: Goldschmidt
authors.forename: T V
authors.initials: TV
authors.lastname: Golovkina
authors.forename: S
authors.initials: S
authors.lastname: Evans
authors.forename: W F
authors.initials: WF
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Thomas-Tikhonenko
mesh_terms: D000208:Acute Disease; D000818:Animals; D002455:Cell Division / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007113:Immunity, Innate; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009336:Necrosis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D014124:Toxoplasmosis, Animal / Q000276:immunology*