Cutting edge: systemic inhibition of angiogenesis underlies resistance to tumors during acute toxoplasmosis.

Document Type

Article

Publication Date

2001

Keywords

Animal, Cell-Division, Cytotoxicity-Immunologic, Endothelium-Vascular, Immunity-Natural, Melanoma-Experimental, Mice, Mice-Inbred-C57BL, Mice-SCID, Necrosis, Neoplasm-Transplantation, Neovascularization, SUPPORT-U-S-GOVT-P-H-S, Toxoplasmosis-Animal

First Page

5878

Last Page

5881

JAX Source

J Immunol 2001 May; 166(10):5878-81.

Grant

AI42334/AI/NIAID, CA71881/CA/NCI

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.

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