Intradermal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic melanoma recruits dendritic cells.
Dendritic cells (DCs) are the main antigen-presenting cells in the skin. We hypothesized that intradermal (i.d.) injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) would recruit DCs into melanoma skin metastases and enhance autologous melanoma antigen presentation to host T cells. Sixteen patients with cutaneous or subcutaneous melanoma metastases were treated with GM-CSF injected i.d. into a single dermal metastasis and into a normal skin site for 10 consecutive days at one of four dose levels (10, 20, 40, or 80 microg/injection). Pretreatment and post-treatment skin and tumor biopsies were stained for a panel of T-cell, B-cell, macrophage, and DC immunohistochemical markers. Positive cells were quantitated in a blinded fashion. There was a significant increase in the number of DCs (HLA-DR+, S100+, factor XIIIa+) and CD45R0+ T cells in the skin and in the tumors Injected with GM-CSF at all dose levels. Uninjected control tumors showed no increase in HLA-DR+ cells or T-cell infiltrate, but did show an Increase in S100+ and factor XIIIa+ cells, suggesting a non-DC population. ID GM-CSF administered in this manner recruited DCs into melanoma tumors and normal skin. Although no antitumor effects were seen, this represents a potential method of preparing skin sites for vaccine delivery.
Nasi
M L
ML
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Lieberman
P
P
Busam
K J
KJ
Prieto
V
V
Panageas
K S
KS
Lewis
J J
JJ
Houghton
A N
AN
Chapman
P B
PB
D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary
D000951:Antigens, Neoplasm; D016178:Granulocyte-Macrophage Colony-Stimulating Factor