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Nature Medicine
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Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells

Nature Medicinevolume 2pages1096–1103 (1996)Cite this article

AnErratum to this article was published on 01 November 1996

Abstract

Inadequate presentation of tumor antigens by host professional antigen–presenting cells (APCs), including dendritic cells (DCs), is one potential mechanism for the escape of tumors from the host immune system. Here, we show that human cancer cell lines release a soluble factor or factors that dramatically affect DC maturation from precursors without affecting the function of relatively mature DCs. One factor responsible for these effects was identified as vascular endothelial growth factor (VEGF). Thus, VEGF may play a broader role in the pathogenesis of cancer than was previously thought, and therapeutic blockade of VEGF action may improve prospects for immunotherapy as well as inhibit tumor neovasculature.

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References

  1. Loannides, C. & Whiteside, T. T cell recognition of human tumors: Implication for molecular immunotherapy of cancer.Clin. Immunol. Immunopathol66, 91–106 (1993).

    Article  Google Scholar 

  2. Cozzolino, F.et al. Characterization of cells from invaded nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphopro-liferative response.J. Exp. Med.166, 303–318 (1987).

    Article CAS  Google Scholar 

  3. Belldegrun, A., Kasid, A., Uppenkamp, M., Topalian, S.L. & Rosenberg, S.A. Human tumor infiltrating lymphocytes: Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy.J. Immunol.42, 4520–4526 (1989).

    Google Scholar 

  4. Gabrilovich, D., Ciernik, F. & Carbone, D.P. Dendritic cells in anti-tumor immune responses. I. Defective antigen presentation in tumor-bearing hosts.Cell. Immunol.170, 101–110 (1996).

    Article CAS  Google Scholar 

  5. Huang, A.Y.C.et al. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens.Science264, 961–965 (1994).

    Article CAS  Google Scholar 

  6. Rock, K.L., Rothstein, L., Gamble, S. & Fleishacker, C. Characterization of antigen-presenting cells that present exogenous antigens in association with class I MHC molecules.J. Immunol.150, 438–446 (1993).

    CAS PubMed  Google Scholar 

  7. Tan, K.C., Hosoi, J., Grabbe, S., Asahina, A. & Granstein, R.D. Epidermal cell presentation of tumor-associated antigens for induction of tolerance.J. Immunol153, 760–767 (1994).

    CAS PubMed  Google Scholar 

  8. Watson, G. & Lopez, D.M. Aberrant antigen presentation by macrophages from tumor-bearing mice is involved in the down-regulation of their T cell responses.J. Immunol.155, 3124–3134 (1995).

    CAS PubMed  Google Scholar 

  9. Alcalay, J. & Kripke, M.L. Antigen-presenting activity of draining lymph node cells from mice painted with a contact allergen during ultraviolet carcinogenesis.J. Immunol.146, 1717–1721 (1991).

    CAS PubMed  Google Scholar 

  10. Erroi, A.et al. IL1 and IL6 released by tumor-associated macrophages from human ovarian carcinoma.Int. J. Cancer41, 65–68 (1989).

    Article  Google Scholar 

  11. Steinman, R.M. The dendritic cell system and its role in immunogenicity.Annu. Rev. Immunol.9, 271–296 (1991).

    Article CAS  Google Scholar 

  12. Knight, S.C. & Stagg, A.J. Antigen-presenting cell types.Curr. Opin. Immunol.5, 374–382 (1993).

    Article CAS  Google Scholar 

  13. Austin, J.M. The dendritic cell system and anti-tumor immunity.In Vivo7, 193–202 (1993).

    Google Scholar 

  14. Zitvogel, L.et al. Therapy of murine tumors with tumor peptide-pulsed dendritic cells: Dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines.J. Exp. Med.183, 87–97 (1996).

    Article CAS  Google Scholar 

  15. Mayordomo, J.I.et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity.Nature Med.1, 1297–1302 (1995).

    Article CAS  Google Scholar 

  16. Hsu, F.J.et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells.Nature Med.2, 52–58 (1996).

    Article CAS  Google Scholar 

  17. Tas, M., Simons, P., Balm, F. & Drexhage, H. Depressed monocyte polarization and clustering of dendritic cells in patients with head and neck cancer: In vitro restoration of this immunosuppression by thymic hormones.Cancer Immunol Immunother.36, 108–114 (1993).

    Article CAS  Google Scholar 

  18. Reynolds, N.J.et al. Down-regulation of Langerhans cell protein kinase C-beta isoenzyme expression in inflammatory and hyperplastic dermatoses.Br. J. Dermatol133, 157–167 (1995).

    Article CAS  Google Scholar 

  19. Bergfelt, L., Emilson, A., Lindberg, M. & Scheynius, A. Quantitative and three-dimensional analysis of Langerhans cells in basal cell carcinoma: A comparative study using light microscopy and confocal laser scanning microscopy.Br. J. Dermatol130, 273–280 (1994).

    Article CAS  Google Scholar 

  20. Toriyama, K., Wen, D.R., Paul, E. & Cochra, A.J. Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin.J. Invest. Dermat.100, 269S–273S (1993).

    Article CAS  Google Scholar 

  21. Gabrilovich, D.I., Nadaf, S., Corak, J., Berzofsky, J.A. & Carbone, D.P. Dendritic cells in anti-tumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice are effective antigen carriers in the therapy of established tumors.Cell Immunol170, 111–120 (1996).

    Article CAS  Google Scholar 

  22. Caux, C., Dezutter-Dambuyant, C., Schmitt, D. & Banchereau, J. GM-CSF and TNF-α cooperate in the generation of dendritic cells.Nature360, 258–261 (1992).

    Article CAS  Google Scholar 

  23. Reid, C.D., Stackpoole, A., Meager, A. & Tikerpae, J. Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow.J. Immunol149, 2681–2688 (1992).

    CAS PubMed  Google Scholar 

  24. Sallusto, F. & Lanzavecchia, A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α.J. Exp. Med.179, 1109–1118 (1994).

    Article CAS  Google Scholar 

  25. Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M. & Heldin, C.-H. Different signal transduction properties of KDR and FLT1, two receptors for vascular endothelial growth factor.J. Biol Chem.269, 26988–26995 (1994).

    CAS PubMed  Google Scholar 

  26. Szabolcs, P.et al. Dendritic cells and macrophages can mature independently from a human bone marrow-derived, post-colony-forming unit intermediate.Blood87, 4520–4530 (1996).

    CAS PubMed  Google Scholar 

  27. Reid, C.D.L.et al. Identification of hematopoietic progenitors of macrophages and dendritic Langerhans cells (DL-CFU) in human bone marrow and peripheral blood.Blood76, 1139–1149 (1990).

    CAS PubMed  Google Scholar 

  28. Roth, P. & Stanley, E.R. The biology of CSF-1 and its receptor.Curr. Topics Microb. Immunol.181, 141–155 (1992).

    CAS  Google Scholar 

  29. Rozenzwajg, M., Canque, B. & Gluckman, J.C. Human dendritic cells differentiation pathway from CD34+ hematopoietic precursor cells.Blood87, 535–544 (1996).

    Google Scholar 

  30. Leung, D.W., Cachianes, G., Kuang, W.-J., Goeddel, D.V. & Ferrara, N. Vascular endothelial growth factor is a secreted angiogenic mitogen.Science246, 1306–1309 (1989).

    Article CAS  Google Scholar 

  31. Connolly, D.T.et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.J. Clin. Invest.84, 1470–1478 (1989).

    Article CAS  Google Scholar 

  32. Takeshita, S.et al. Therapeutic angiogenesis: A single intra-arterial bolus of vascular endothelial growth factor augments revascularization in a rabbit is chemic hind limb model.J. Clin. Invest.93, 662–670 (1994).

    Article CAS  Google Scholar 

  33. Ferrara, N., Houck, K., Jakeman, J. & Leung, D.W. Molecular and biological properties of the vascular endothelial growth factor family of proteins.Endocrine Rev.13, 18–32 (1992).

    Article CAS  Google Scholar 

  34. Kondo, S., Asano, M., Matsuo, K., Ohmori, I. & Suzuki, H. Vascular endothelial growth factor/vascular permeability factor is detectable in the sera of tumor-bearing mice and cancer patients.Biochem. Biophys. Acta1221, 211–214 (1994).

    Article CAS  Google Scholar 

  35. Takano, S.et al. Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients.Cancer Res.56, 2185–2190 (1996).

    CAS PubMed  Google Scholar 

  36. Shen, H.et al. Characterization of vascular permeability factor/vascular endothelial growth factor receptors on mononuclear phagocytes.Blood81, 2767–2773 (1993).

    CAS PubMed  Google Scholar 

  37. Hoehn, G.T.et al. Tnk1: A novel intracellular tyrosine kinase gene isolated from human umbilical cord CD34+/Lin/CD38 stem/progenitor cells.Oncogene12, 903–913 (1996).

    CAS PubMed  Google Scholar 

  38. Katoh, O., Tauchi, H., Kawaishi, K., Kimura, A. & Satow, Y. Expression of the vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation.Cancer Res.55, 5687–5692 (1995).

    CAS PubMed  Google Scholar 

  39. Broxmeyer, H.E.et al. Myeloid progenitor cells regulatory effects of vascular endothelial cell growth factor.Inter. J. Hematol.62, 203–215 (1995).

    Article CAS  Google Scholar 

  40. Axelsson, K.et al. Tumor angiogenesis as a prognostic assay for invasive due tal breast carcinoma.J. Natl. Cancer Inst.87, 997–1008 (1995).

    Article CAS  Google Scholar 

  41. Bossi, P.et al. Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations.Cancer Res.55, 5049–5053 (1995).

    CAS PubMed  Google Scholar 

  42. Bochner, B.H.et al. Angiogenesis in bladder cancer: Relationship between microvessel density and tumor prognosis: Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma.J. Natl. Cancer Inst.87, 1603–1612 (1995).

    Article CAS  Google Scholar 

  43. Gazdar, A.F. & Oie, H.K. Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium.Cancer Res.46, 6011–6012 (1986).

    CAS PubMed  Google Scholar 

  44. Bhardwaj, N.et al. Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells.J. Clin. Invest.94, 797–807 (1994).

    Article CAS  Google Scholar 

  45. Hayhoe, F.G.J. & Quaglino, D.Haematological Cytochemistry. (Churchill Livingston, London, 1998).

    Google Scholar 

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Author information

Author notes
  1. Dmitry I. Gabrilovich, Sorena Nadaf & David P. Carbone

    Present address: The Vanderbilt Cancer Center, Vanderbilt University School of Medicine, 649 Medical Research Building II, Nashville, Tennessee, 37232-6838, USA

Authors and Affiliations

  1. Hamon Center for Therapeutic Oncology Research and the Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas, 75325, USA

    Dmitry I. Gabrilovich, Hailei L. Chen, Khaled R. Girgis, H. Thomas Cunningham, Geralyn M. Meny, Sorena Nadaf, Denise Kavanaugh & David P. Carbone

Authors
  1. Dmitry I. Gabrilovich

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  7. Denise Kavanaugh

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Gabrilovich, D., Chen, H., Girgis, K.et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells.Nat Med2, 1096–1103 (1996). https://doi.org/10.1038/nm1096-1096

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