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

Cancer Res. 2004 Nov 15;64(22):8456-60. doi: 10.1158/0008-5472.CAN-03-3251.

Abstract

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Dendritic Cells / immunology*
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Middle Aged
  • Sentinel Lymph Node Biopsy*
  • Single-Blind Method

Substances

  • Adjuvants, Immunologic
  • Granulocyte Colony-Stimulating Factor