Differences in Dendritic Cells Stimulated in Vivo by Tumors Engineered to Secrete Granulocyte-Macrophage Colony-stimulating Factor or Flt3-Ligand

N Mach, S Gillessen, SB Wilson, C Sheehan, M Mihm… - Cancer research, 2000 - AACR
N Mach, S Gillessen, SB Wilson, C Sheehan, M Mihm, G Dranoff
Cancer research, 2000AACR
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 …
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 Th1 response elicited by FL. DCs generated by GM-CSF were CD8α 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.
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