Abstract
The interferon (IFN)-γ–induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer (NK) cells in mice1,2. Here we show that the main source of IFN-γ is not the conventional NK cell but a subset of B220+Ly6C− dendritic cells, which are atypical insofar as they express NK cell-surface molecules. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220+NK1.1+ dendritic cells secrete high levels of IFN-γ and mediate TRAIL-dependent lysis of tumor cells. Adoptive transfer of these IFN-producing killer dendritic cells (IKDCs) into tumor-bearing Rag2−/−Il2rg−/− mice prevented tumor outgrowth, whereas transfer of conventional NK cells did not. In conclusion, we identified IKDCs as pivotal sensors and effectors of the innate antitumor immune response.
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Acknowledgements
We thank F. Housseau for communicating his data on IKDCs and providing reagents, J. Tschopp (University of Lausanne) and G. Salvesen (Burnham Institute) for providing plasmids and M.L. Albert (Pasteur Institute) for providing reagents. J. Taieb is supported by a Poste d'accueil INSERM and AP-HP, and N. Chaput is supported by a European fellowship (QLRT-2001-00093) and by the Association for Research Against Cancer (ARC). E. Ullrich was supported by the Deutsche Forschungsgemeinschaft and M. Bonmort by the Poste d' Accueil INSERM. This work was also supported by EU grants (ALLOSTEM, DC THERA), ARC and the Ligue Nationale contre le Cancer (équipes labelisées de G.K. and L.Z).
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Supplementary information
Supplementary Fig. 1
Regressing tumors are invaded by CD11c+B220+Gr1− cells. (PDF 380 kb)
Supplementary Fig. 2
Phenotypic analyses of B220+NK1.1+ DCs in spleens of naive mice. (PDF 37 kb)
Supplementary Fig. 3
Localization of IKDCs in vivo. (PDF 31 kb)
Supplementary Fig. 4
The IFN-γ receptor is crucial for the antitumor effects mediated by imatinib mesylate +IL-2. (PDF 27 kb)
Supplementary Fig. 5
IKDCs are functional in Rag2−/−Il2rg−/− mice. (PDF 28 kb)
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Taieb, J., Chaput, N., Ménard, C. et al. A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med 12, 214–219 (2006). https://doi.org/10.1038/nm1356
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DOI: https://doi.org/10.1038/nm1356
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