Regional lymphatic immunity in melanoma

Melanoma is an immunogenic tumor that has developed methods to successfully evade immune recognition, while paradoxically spreading through the lymphatic system. Increasing evidence supports that melanoma-derived factors suppress regional immunity within the host. At a very early stage, melanoma communicates with the tumor-draining lymph nodes, and prepares them for seeding of metastatic disease by stimulating lymphangiogenesis and downregulation of the sentinel lymph node immunity well before the malignant cells arrive. Investigations have demonstrated that the induction of suppressor cells, peripheral tolerance, and a less tumor-responsive Th2 cytokine environment may provide a hospitable environment for subsequent lymphatic metastasis. Patients with early-stage disease may benefit from the restoration of the regional immune function to a level that controls the progression of residual occult metastases and ensures a durable clinical response. Herein we provide a succinct summary of the current progress in this field in order to guide future investigations.