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Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells

Nature Medicine volume 7, pages 1339–1346 (2001)Cite this article

Abstract

Dendritic-cell (DC) trafficking and function in tumors is poorly characterized, with studies confined to myeloid DCs (DC1s). Tumors inhibit DC1 migration and function, likely hindering specific immunity. The role of plasmacytoid DCs (DC2s) in tumor immunity is unknown. We show here that malignant human ovarian epithelial tumor cells express very high levels of stromal-derived factor-1, which induces DC2 precursor (preDC2) chemotaxis and adhesion/transmigration, upregulates preDC2 very late antigen (VLA)-5, and protects preDC2s from tumor macrophage interleukin-10–induced apoptosis, all through CXC chemokine receptor-4. The VLA-5 ligand vascular-cell adhesion molecule-1 mediated preDC2 adhesion/transmigration. Tumor preDC2s induced significant T-cell interleukin-10 unrelated to preDC2 differentiation or activation state, and this contributed to poor T-cell activation. Myeloid precursor DCs (preDC1s) were not detected. Tumors may weaken immunity by attracting preDC2s and protecting them from the harsh microenvironment, and by altering preDC1 distribution.

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Figure 1: Freshly isolated DCs in malignant ascites of patients with ovarian carcinoma display flow cytometric, morphologic and functional characteristics of preDC2s.
Figure 2: Ovarian epithelial carcinoma cells express functional SDF-1.
Figure 3: Tumor and blood preDC2s activate T cells in distinct manners when freshly isolated and following differentiation with IL-3.
Figure 4: Tumor preDC2s induce significant T-cell IL-10 induction independent of differentiation or activation status.

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Acknowledgements

We thank O. Haller for antibody against MxA; A. Amara and F. Arenzana-Seisdedos for monoclonal antibody K15C against SDF-1; and S. Clayton, E. Kraus, S. Coquery, C. Chalouni and D. Olivares for technical assistance. T.J.C. was supported by grants from the NIH, the Baylor endowment and Golfers against Cancer. D.E., V.M. and P.G. were supported by the Association de Recherche sur le Cancer (ARC), France.

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Authors and Affiliations

  1. Tulane Medical School, Section of Hematology and Medical Oncology, New Orleans, Louisiana, USA

    Weiping Zou, Shuang Wei & Tyler J. Curiel

  2. Baylor Institute for Immunology Research, Dallas, Texas, USA

    Weiping Zou, Jozef Borvak, Tatyana Isaeva & Shuang Wei

  3. INSERM, U-355, Institut Paris-Sud sur les Cytokines, Clamart, France

    Véronique Machelon & Françoise Nome

  4. Service d'Anatomie Pathologique, Hôpital Antoine Béclère, Clamart, France

    Aurore Coulomb-L'Hermin & Frédérique Capron

  5. Institut Paris-Sud sur les Cytokines, INSERM U 131, Clamart, France

    Roman Krzysiek, Ingrid Durand-Gasselin, Pierre Galanaud & Dominique Emilie

  6. Baylor University Medical Center, Dallas, Texas, USA

    Alan Gordon

  7. Wallace Tumor Institute, University of Alabama, Birmingham, Alabama, USA

    Terri Pustilnik & David T. Curiel

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Correspondence to Weiping Zou or Tyler J. Curiel.

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Zou, W., Machelon, V., Coulomb-L'Hermin, A. et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 7, 1339–1346 (2001). https://doi.org/10.1038/nm1201-1339

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