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A critical function for type I interferons in cancer immunoediting

Nature Immunology volume 6, pages 722–729 (2005)Cite this article

A Corrigendum to this article was published on 01 August 2005

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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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Figure 1: Rejection of highly immunogenic Rag2−/− regressor sarcomas is blocked by treatment of wild-type mice with mAb MAR1-5A3 to IFNAR1.
Figure 2: Increased incidence of MCA-induced tumors in IFNα/β-unresponsive mice.
Figure 3: A subset of Ifnar1−/− MCA sarcomas show high immunogenicity and are rejected in immunocompetent hosts.
Figure 4: Tumor cell IFNα/β sensitivity is not required for the induction of lymphocyte-mediated tumor rejection.
Figure 5: Ifnar1−/− progressor tumors still grow progressively even when rendered responsive to IFNα/β.
Figure 6: Rag2−/− regressor tumors grow progressively in Ifnar1−/− recipients.
Figure 7: IFNα/β-responsive hematopoietic cells are sufficient for mediation of tumor rejection.
Figure 8: IFNα/β-responsive hematopoietic cells are required for mediation of tumor rejection.
Figure 9: Tumor rejection in radiation chimeras is not due to the development of an abnormal hyper-reactive immunological state.

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  • 24 June 2005

    Changed label on Fig. 4a and 4c

Notes

  1. 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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  1. Gavin P Dunn and Allen T Bruce: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    Gavin P Dunn, Allen T Bruce, Kathleen C F Sheehan, Vijay Shankaran, Ravindra Uppaluri, Jack D Bui, Mark S Diamond, Catherine M Koebel, Cora Arthur, J Michael White & Robert D Schreiber

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Correspondence to Robert D Schreiber.

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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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