title: Immunomodulation of the melanoma sentinel lymph node: a novel adjuvant therapeutic option.
abstract: Cutaneous melanoma is the most aggressive type of skin cancer. Paradoxically, melanoma is also the most immunogenic tumour identified to date: tumour-reactive T cells are detectable both in the blood and in tumour-draining lymph nodes (TDLN) of melanoma patients and their frequency can be increased by specific vaccination. However, early melanoma development is accompanied by impaired immune effector functions in the initial TDLN, the sentinel lymph node (SLN). Most notably, a reduced frequency and activation state of dendritic cells (DC) interferes with the uptake and presentation of tumour-associated antigens (TAA) to specific anti-tumour cytotoxic T-lymphocytes (CTL) and T helper cells (Th). These impaired immune effector functions may contribute to the early metastatic events that are associated with this tumour type. Since complete surgical excision at an early stage remains the only curative treatment option (adjuvant therapy options are limited and show no survival benefits), immunopotentiation of the SLN to jump-start or boost tumour specific immunity in early stage melanoma may be a valuable adjuvant treatment option that can be generally applied with minimal discomfort to the patient. Early clinical studies indicate that local Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF) or Cytosine-phosphate-Guanine (CpG) administration leads to activation of different DC subsets and conditions the SLN microenvironment to be more conducive to the generation of T-cell-mediated anti-tumour immunity.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Molenkamp
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Berbel J R
authors.initials: BJ
authors.lastname: Sluijter
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007155:Immunologic Factors