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Scientific article
English

Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand

Published inCancer research, vol. 60, no. 12, p. 3239-3246
Publication date2000-06-15
Abstract

Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and flt3-ligand (FL) induce the development of dendritic cells (DCs). To compare the functional properties of DCs stimulated by these cytokines in vivo, we used retroviral-mediated gene transfer to generate murine tumor cells secreting high levels of each molecule. Injection of tumor cells expressing either GM-CSF or FL resulted in the dramatic increase of CD11c+ cells in the spleen and tumor infiltrate. However, vaccination with irradiated, GM-CSF-secreting tumor cells stimulated more potent antitumor immunity than vaccination with irradiated, FL-secreting tumor cells. The superior antitumor immunity elicited by GM-CSF involved a broad T cell cytokine response, in contrast to the limited Thl response elicited by FL. DCs generated by GM-CSF were CD8alpha- and expressed higher levels of B7-1 and CD1d than DCs cells generated by FL. Injection sites of metastatic melanoma patients vaccinated with irradiated, autologous tumor cells engineered to secrete GM-CSF demonstrated similar, dense infiltrates of DCs expressing high levels of B7-1. These findings reveal critical differences in the abilities of GM-CSF and FL to enhance the function of DCs in vivo and have important implications for the crafting of tumor vaccines.

eng
Keywords
  • Adjuvants, Immunologic / metabolism
  • Animals
  • Antigens, CD1 / metabolism
  • Antigens, CD1d
  • CD8 Antigens / metabolism
  • Cancer Vaccines
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Flow Cytometry
  • Gene Transfer Techniques
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Integrin alphaXbeta2 / metabolism
  • Interleukin-5 / metabolism
  • Melanoma / immunology
  • Melanoma / therapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Retroviridae / genetics
  • Spleen / immunology
  • T-Lymphocytes / immunology
  • Th1 Cells / immunology
  • Time Factors
  • Tumor Cells, Cultured
Affiliation Not a UNIGE publication
Citation (ISO format)
MACH, Nicolas et al. Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. In: Cancer research, 2000, vol. 60, n° 12, p. 3239–3246.
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0008-5472
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