An essential role of Th1 responses and interferon gamma in infection-mediated suppression of neoplastic growth.

Abstract

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

• Authors: Erinn B Rankin, Duonan Yu, Jiu Jiang, Hao Shen, Edward J Pearce, Michael H Goldschmidt, David E Levy, Tatyana V Golovkina, Christopher A Hunter, Andrei Thomas-Tikhonenko
• Journal: Cancer biology & therapy (Cancer Biol Ther) 2003 Nov-Dec Vol. 2 Issue 6 Pg. 687-93 ISSN: 1538-4047 [Print] United States
• PMID: 14688478 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Culture Media, Conditioned
• Cytokines
• Drug Combinations
• Laminin
• Proteoglycans
• Vascular Endothelial Growth Factor A
• matrigel
• Interleukin-10
• Interferon-gamma
• Collagen

Topics

• Acute Disease
• Animals
• Cell Line, Tumor
• Cell Transplantation
• Clone Cells
• Collagen (metabolism)
• Culture Media, Conditioned (analysis)
• Cytokines (immunology)
• Drug Combinations
• Infections (blood, immunology)
• Interferon-gamma (analysis, immunology)
• Interleukin-10 (deficiency)
• Laminin (metabolism)
• Listeria monocytogenes (pathogenicity)
• Lymphocytic choriomeningitis virus (pathogenicity)
• Melanoma, Experimental (blood, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Biological
• Neovascularization, Pathologic
• Proteoglycans (metabolism)
• Th1 Cells (immunology)
• Time Factors
• Toxoplasma (pathogenicity)
• Toxoplasmosis
• Vascular Endothelial Growth Factor A (analysis, genetics, metabolism)