Local administration of granulocyte/macrophage colony-stimulating factor increases the number and activation state of dendritic cells in the sentinel lymph node of early-stage melanoma.
The initial tumor-draining lymph node, the sentinel lymph node, not only constitutes the first expected site of micrometastasis but also the first point of contact between tumor-associated antigens and the adaptive immune system. A tumor-induced decrease in the frequency and activation state of sentinel lymph node dendritic cells will impair the generation of effective antitumor T-cell responses and increase the likelihood of metastatic spread. Here, we demonstrate that intradermal administration of granulocyte macrophage-colony stimulating factor around the excision site of stage I primary melanoma tumors increases the number and activation state of dendritic cells in the paracortical areas of the sentinel lymph node and enhances their binding to T cells. We conclude that local treatment of melanoma patients with granulocyte macrophage-colony stimulating factor, before surgery, conditions the sentinel lymph node microenvironment to enhance mature dendritic cell recruitment and hypothesize that this may be more conducive to the generation of T-cell-mediated antitumor immunity.
Vuylsteke
Ronald J C L M
RJ
Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Molenkamp
Barbara G
BG
Gietema
Hester A
HA
van Leeuwen
Paul A M
PA
Wijnands
Pepijn G J T B
PG
Vos
Wim
W
van Diest
Paul J
PJ
Scheper
Rik J
RJ
Meijer
Sybren
S
de Gruijl
Tanja D
TD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D021701:Sentinel Lymph Node Biopsy; D016037:Single-Blind Method
D000276:Adjuvants, Immunologic; D016179:Granulocyte Colony-Stimulating Factor