The Lymphatic Vascular System in Extracellular Vesicle-Mediated Tumor Progression

Tumor growth and progression require molecular interactions between malignant and host cells. In recent years, extracellular vesicles (EVs) emerged as an important pillar of such interactions, carrying molecular information from their donor cells to distant recipient cells. Thereby, the phenotype and function of the recipient cells are altered, which may facilitate tumor immune escape and tumor metastasis to other organs through the formation of pre-metastatic niches. A prerequisite for these effects of tumor cell-derived EVs is an efficient transport system from the site of origin to the body periphery. Here, we highlight the role of the lymphatic vascular system in the distribution and progression-promoting functions of tumor cell-derived EVs. Importantly, the lymphatic vascular system is the primary drainage system for interstitial fluid and its soluble, particulate, and cellular contents, and therefore represents the principal route for regional (i.e., to tumor-draining lymph nodes) and systemic distribution of EVs derived from solid tumors. Furthermore, recent studies highlighted the tumor-draining lymph node as a crucial site where tumor-derived EVs exert their effects. A deeper mechanistic understanding of how EVs gain access to the lymphatic vasculature, how they interact with their recipient cells in tumor-draining lymph nodes and beyond, and how they induce phenotypic and functional maladaptation will be instrumental to identify new molecular targets and conceive innovative approaches for cancer therapy.