Role of lymphatic vasculature in regional and distant metastases

•Lymphangiogenesis facilitates seeding of distant metastases and organ colonization.•LECs control entry and exit of tumor cells from the lymphatic vessels by chemokines.•LECs directly modulate immune response and mediate immunosuppression.

In cancer, lymphatic vasculature has been traditionally viewed only as a transportation system for metastatic cells. It has now become clear that lymphatics perform many additional functions which could influence cancer progression. Lymphangiogenesis, induced at the primary tumor site and at distant sites, potently augments metastasis. Lymphatic endothelial cells (LECs) control tumor cell entry and exit from the lymphatic vessels. LECs also control immune cell traffic and directly modulate adaptive immune responses. This review highlights advances in our understanding of the mechanisms by which lymphatic vessels, and in particular lymphatic endothelium, impact metastasis.