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- Title
Sustained low-level expression of interferon-γ promotes tumor development: potential insights in tumor prevention and tumor immunotherapy.
- Authors
Yu-Fei He; Xiao-Hong Wang; Gui-Mei Zhang; Hong-Tao Chen; Hui Zhang; Zuo-Hua Feng
- Abstract
Although the proinflammatory cytokine interferon-γ (IFN-γ) has been generally thought to enhance antitumor immune responses and be involved in antitumor mechanisms of many other immunotherapy molecules, it has also been reported that IFN-γ could promote tumor immune evasion. In this report, by using an ideal mouse model that expresses IFN-γ locally in muscle, we demonstrate that sustained low-level expression of IFN-γ promotes the development of several types of tumor including H22 hepatoma, MA782/5S mammary adenocarcinoma and B16 melanoma. However, transitory expression of IFN-γ does not have such an effect. On the other hand, sustained high-level expression of IFN-γ mediates significant antitumor effect on H22 hepatoma. Low level of IFN-γ upregulates expression of PD-L1, PD-L2, CTLA-4 and Foxp3, which may partly account for the tumor immune evasion promoted by IFN-γ. Furthermore, blockade of PD-L inhibits IFN-γ’s tumor-promoting effect. Our findings provide a mechanistic link between chronic inflammation and cancer and would have potential implications for cancer prevention and also for the design of cytokine–based cancer immunotherapy.
- Subjects
INTERFERONS; CANCER immunotherapy; CYTOKINES; ANTINEOPLASTIC agents; COCARCINOGENESIS; CANCER treatment; CANCER immunology; CANCER prevention
- Publication
Cancer Immunology, Immunotherapy, 2005, Vol 54, Issue 9, p891
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-004-0654-1