Abstract
'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-γ (IFN-γ) is known to be involved in this process, the involvement of type I interferons (IFN-α/β) has not been elucidated. We now show that, like IFN-γ, endogenously produced IFN-α/β was required for the prevention of the growth of primary carcinogen–induced and transplantable tumors. Although tumor cells are important IFN-γ targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-α/β targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-γ.
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Change history
24 June 2005
Changed label on Fig. 4a and 4c
Notes
NOTE: In the version of this article initially published online, the graphs in Figure 4a,c were labeled incorrectly. The graphs are labeled correctly here. The error has been corrected in the HTML version of the article. This correction has been appended to the PDF and print versions.
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Acknowledgements
We thank L. Old of the Ludwig Institute for Cancer Research; members of the Schreiber laboratory for discussions throughout this work; W. Yokoyama and M. Orihuela and the Speed Congenics Core facility of the Rheumatic Diseases Core Center at Washington University for genetic marker analyses; and D. Kreamalmeyer, K. Kooi and T. Irwin for assistance with animal work. Supported by the National Cancer Institute (CA43059 and CA107527), Ludwig Institute for Cancer Research and Cancer Research Institute.
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Supplementary information
Supplementary Fig. 1
Selective reconsitution of IFNγ or IFNα/β responsiveness in the GAR4 tumor. (PDF 53 kb)
Supplementary Fig. 2
Microsatellite analysis indicates that IFNAR−/− mice are on the 129/SvPAS (129S2) genetic background. (PDF 127 kb)
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Dunn, G., Bruce, A., Sheehan, K. et al. A critical function for type I interferons in cancer immunoediting. Nat Immunol 6, 722–729 (2005). https://doi.org/10.1038/ni1213
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DOI: https://doi.org/10.1038/ni1213
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