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, 2000•AACRBoth 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 …
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.
AACR