Experimental frontiers for clinical applications: novel approaches to understanding mechanisms of lymph node metastases in melanoma.

Sentinel lymph nodes are the first nodes to receive lymph from primary tumors and are the preferential site of initial metastases. Sentinel nodes show morphology changes that suggests immune modulation with reduced antigen-presenting dendritic cells, activated T lymphocytes, high endothelial venules and transvenular migration of T lymphocytes. Tumor cells generate down-regulatory molecules. We postulate that tumor-induced immune dysfunction facilitates establishment of nodal metastases. Nodal immune modulation can be reversed by granulocyte macrophage colony-stimulating factor (GMCSF), a finding with implications for future therapy to prevent or reverse these nodal metastases.