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

The ability of various infections to suppress neoplastic growth has been we ll documented. This phenomenon has been traditionally attributed to infecti on-induced concomitant, cell-mediated antitumor immunity. We found that inf ection with Toxoplasma gondii effectively blocked neoplastic growth of a no nimmunogenic B16.F10 melanoma. Moreover, this effect was independent of cyt otoxic T or NK cells, production of NO by macrophages, or the function of t he cytokines IL-12 and TNF-alpha. These findings suggested that antitumor c ytotoxicity 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 se vere hypoxia and avascular necrosis that are incompatible with progressive neoplastic growth. Our results identify the suppression of tumor neovascula rization as a novel mechanism critical for infection-induced resistance to tumors.