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Dendritic cells directly trigger NK cell functions: Cross-talk relevant in innate anti-tumor immune responses in vivo

Nature Medicine volume 5, pages 405–411 (1999)Cite this article

Abstract

Cytotoxic T lymphocytes and natural killer cells are essential effectors of anti-tumor immune responses in vivo. Dendritic cells (DC) 'prime' tumor antigen-specific cytotoxic T lymphocytes; thus, we investigated whether DC might also trigger the innate, NK cell-mediated anti-tumor immunity. In mice with MHC class I-negative tumors, adoptively transferred- or Flt3 ligand-expanded DC promoted NK cell-dependent anti-tumor effects. In vitro studies demonstrated a cell-to-cell contact between DC and resting NK cells that resulted in a substantial increase in both NK cell cytolytic activity and IFN-γ production. Thus, DC are involved in the interaction between innate and adaptive immune responses.

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Figure 1: FL induces NK cell-dependent anti-tumor effects in an MHC class I-negative mesothelioma.
Figure 2: Neither type I IFNs nor IL-12 are involved in FL-mediated anti-tumor effects.
Figure 3: Role of the lymphoid-related DC subset.
Figure 4: DC directly stimulate NK cytolytic activity in vitro.
Figure 5: Cell contact requirement and specificity of the DC/NK cell interaction.
Figure 6: Adoptive transfer of D1 dendritic cells in B6-nude mice with AK7 tumors.

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Acknowledgements

We are grateful to the staff of the Animal Facility of IGR. We thank C. Maliszewski, C. Bonnerot, S. Amigorena, F. Faure and E. Vivier for critical review of the manuscript. We are also indebted to M. Rescigno for contribution with the R1-conditioned medium and to P. Bousso for his input in flow cytometry analyses. E. Mottez is acknowledged for the generation of the P815-B7.1 cell line. This work was supported by the Association pour la Recherche sur le Cancer, the Ligue Nationale de Lutte contre le Cancer, the GEFLUC association, programme "Immunité Antitumorale", the Institut Gustave Roussy, CRC IGR number 97.1, and by CNRS. NF was supported by the Institut de Formation Supérieure Biomédicale, the Fondation pour la Recherche Médicale and Rhône Poulenc RORER. AL was supported by CRC IGR number 97.1.

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Authors and Affiliations

  1. Département de Biologie Clinique, Unité d'Immunologie, Villejuif, France

    Nadine C. Fernandez, Anne Lozier, Caroline Flament, Dominique Bellet & Laurence Zitvogel

  2. CNRS-UMR1582, Institut Gustave Roussy, Villejuif, France

    Michel Perricaudet

  3. Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy

    Paola Ricciardi-Castagnoli

  4. University Institut for Virology, Zürich, Switzerland

    Mark Suter

  5. Department of Immunobiology, Immunex Corporation, Seattle, 98101-2936, Washington, USA

    Eugene Maraskovsky

  6. Ludwig Oncology Unit, Austin and Repatriation Medical Center, Heidelberg, Australia

    Eugene Maraskovsky

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  1. Nadine C. Fernandez
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Correspondence to Laurence Zitvogel.

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Fernandez, N., Lozier, A., Flament, C. et al. Dendritic cells directly trigger NK cell functions: Cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5, 405–411 (1999). https://doi.org/10.1038/7403

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