Melanoma exosomes enable tumor tolerance in lymph nodes

Melanoma preferentially spreads via lymph nodes. Melanoma exosomes can induce angiogenesis and immune suppression. However, a role for melanoma exosomes in facilitating tumor tolerance in lymph nodes has not been considered. Herein, the hypothesis that melanoma exosome mediated induction of vascular endothelial cell (VEC) derived tumor necrosis factor alpha (TNF-α) results in lymphatic endothelial cell (LEC) mediated tumor tolerance is explored. To support this hypothesis, experiments involving ex vivo lymph node associated VECs, LECs, dendritic cells and T lymphocytes are proposed based upon a previously established fluorescent exosome lymph node trafficking model. The implication of the hypothesis in the context of melanoma exosome mediated induction of tumor tolerance in lymph nodes is then discussed.