Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect.

Simple Summary: Lymphatic vessels are low-pressure, blind-ended tubular structures essential in maintaining tissue fluid homeostasis, immune cell transport, and lipid transport. More and more evidence showed that lymphangiogenesis might be closely related to the development of many diseases, and the intervention of lymphangiogenesis may be a new direction of disease treatment. This review aims to discuss the molecular mechanisms of lymphangiogenesis, the effect of lymphangiogenesis on tumor immune tolerance, the emerging role of meningeal lymphatics and cardiac lymphatics, and the promising applications of lymphangiogenesis in immunotherapy and bioengineering materials. The lymphatic system is a channel for fluid transport and cell migration, but it has always been controversial in promoting and suppressing cancer. VEGFC/VEGFR3 signaling has long been recognized as a major molecular driver of lymphangiogenesis. However, many studies have shown that the neural network of lymphatic signaling is complex. Lymphatic vessels have been found to play an essential role in the immune regulation of tumor metastasis and cardiac repair. This review describes the effects of lipid metabolism, extracellular vesicles, and flow shear forces on lymphangiogenesis. Moreover, the pro-tumor immune tolerance function of lymphatic vessels is discussed, and the tasks of meningeal lymphatic vessels and cardiac lymphatic vessels in diseases are further discussed. Finally, the value of conversion therapy targeting the lymphatic system is introduced from the perspective of immunotherapy and pro-lymphatic biomaterials for lymphangiogenesis. [ABSTRACT FROM AUTHOR]