An Essential Role of Th1 Responses and Interferon-gamma in Infection-Mediated Suppression of Neoplastic Growth

• DOI: 10.4161/cbt.2.6.557
• Publication Date: 2011-02-03T21:19:13Z
• Authors: Erinn B. Rankin; Duonan Yu
• Keywords: Neoplastic transformation

We had previously demonstrated that in mice acute toxoplasmosis leads to systemic inhibition of angiogenesis and, consequently, strong suppression neoplastic growth. Here we investigated the role Th1 cytokines, particular interferon gamma (IFN-gamma), this phenomenon. Besides toxoplasma, growth was readily blocked during infection with other response-inducing pathogens such as Listeria monocytogenes and lymphocytic choriomeningitis virus (LCMV). In contrast, chronic LCMV (when responses were strongly suppressed) Schistosoma mansoni Th2 predominated) afforded no anti-tumor protection. To corroborate involvement cytokines infection-mediated growth, utilized deficient interleukin-10 (IL10), a suppressor responses. When challenged B16 cells concomitantly toxoplasma infection, both IL10-null wild type exhibited resistance However, tumors borne by animals even smaller than those their counterparts. This enhanced correlated dramatically elevated levels circulating IFN-gamma, principal cytokine. Furthermore, while interleukin-12 tumor necrosis factor dispensable for suppression, IFN-gamma production or signaling, neovascularization markedly enhanced. Interestingly, enhancement also apparent uninfected suggesting its anti-angiogenic effects underlie infection-dependent -independent surveillance.