Granulocyte-macrophage colony-stimulating factor gene transfer to dendritic cells or epidermal cells augments their antigen-presenting function including induction of anti-tumor immunity

Hiroaki Ozawa, Wanhong Ding, Hideshi Torii, Junichi Hosoi, Kristina Seiffert, Kristina Campton, Neil R. Hackett, Norbert Topf, Ronald Crystal, Richard D. Granstein

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22 Citations (Scopus)

Abstract

Dendritic antigen-presenting cells derived from epidermis (Langerhans cells), bone marrow, and peripheral blood can present a wide variety of antigens, including tumor-associated antigens, for various immune responses. The development and function of dendritic cells is dependent upon a number of cytokines including granulocyte-macrophage-colony-stimulating factor. For example, Langerhans cells can present tumor-associated antigens for the induction of substantial in vivo antitumor immunity but only after activation in vitro by granulocyte-macrophage-colony-stimulating factor. Thus, we reasoned that insertion of a cDNA for granulocyte-macrophage-colony- stimulating factor into dendritic antigen-presenting cells may allow for autocrine stimulation and increased antigen-presenting capability. To test this possibility, we utilized an adenovirus vector to insert a cDNA for murine granulocyte-macrophage-colony-stimulating factor into the dendritic cell lines XS52-4D and XS106 (derived from neonatal mouse epidermis), bone marrow-derived dendritic cells, and epidermal cells that contain Langerhans cells. Infection of each of these cell types resulted in release of abundant quantities of granulocyte-macrophage-colony-stimulating factor. XS52-4D and XS106 cells infected with adenovirus granulocyte-macrophage-colony- stimulating factor exhibited prolonged dendrites and greater expression of major histocompatibility complex class II molecules and CD86 compared with cells infected with a null vector. Granulocyte-macrophage-colony-stimulating factor cDNA-containing XS cells, bone marrow-derived dendritic cells, and epidermal cells had more potent alloantigen presenting capability than cells infected with a null vector. Most importantly, granulocyte-macrophage-colony- stimulating factor gene-transferred epidermal cells were able to present tumor-associated antigens for in vivo anti-tumor immunity against challenge with the S1509a spindle-cell tumor whereas null vector-infected cells were unable to prime for immunity. These results suggest that introduction of a cDNA for granulocyte-macrophage-colony-stimulating factor into dendritic cells may be an effective means to augment their antigen-presenting capability and that granulocyte-macrophage-colony-stimulating factor gene- transferred epidermal cells may be useful in tumor vaccination strategies.

Original languageEnglish
Pages (from-to)999-1005
Number of pages7
JournalJournal of Investigative Dermatology
Volume113
Issue number6
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

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Keywords

  • Antigen presentation
  • Dendritic cells
  • Immunotherapy
  • Tumor immunity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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