Granulocyte–Macrophage Colony-Stimulating Factor Gene Transfer to Dendritic Cells or Epidermal Cells Augments Their Antigen-Presenting Function Including Induction of Anti-Tumor Immunity

• Published in: Journal of investigative dermatology Vol. 113; no. 6; pp. 999 - 1005
• Main Authors: Ozawa, Hiroaki, Ding, Wanhong, Torii, Hideshi, Hosoi, Junichi, Seiffert, Kristina, Campton, Kristina, Granstein, Richard D., Hackett, Neil R., Topf, Norbert, Crystal, Ronald G.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Danvers, MA Elsevier Inc 01-12-1999; Nature Publishing
• Subjects: Animals; Antigen Presentation; Antigens, Neoplasm - immunology; Biological and medical sciences; dendritic cells; Dendritic Cells - physiology; Dermatology; Epidermis - immunology; Female; Gene Transfer Techniques; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Immunization; immunotherapy; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Neoplasms, Experimental - immunology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; tumor immunity; tumor immunity; dendritic cells; antigen presentation; immunotherapy; Dendritic cell; Antigen presentation; Cell line; Polypeptide; Immunotherapy; Cytokine; Epidermis; Keratinocyte; Skin; Anticarcinogen; Biological activity; Granulocyte macrophage colony stimulating factor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.1999.00769.x

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 anti-tumor 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-transfer- red epidermal cells may be useful in tumor vaccination strategies.