Lymphatic Endothelial Cells and Organ-Associated Lymphangiogenesis in Tumor Microenvironment

Lymphatic vessels are a kind of heterogeneous and versatile component of the lymphatic system, with a unique ability to respond to environmental changes in different organs. The heterogeneity and plasticity of lymphatic endothelial cells (LECs) and defective lymphatic architecture are critical for organ-specific lymphatic function. Moreover, lymphatic vessels have a dual effect on tumor microenvironment (TME), and lymphangiogenesis, an active and dynamic player, is a hallmark of cancer progression and treatment resistance. Dysregulation of lymphatic vessels and uncontrolled lymphangiogenesis contribute to the pathogenesis of many diseases, including cancer. Increasing evidence has indicated that lymphangiogenesis provides a critical target for inhibiting lymphatic metastasis, in which immune checkpoint inhibitors, either alone or combined with chemotherapy, may have a therapeutic value. This article reviews the current status of tumor-associated lymphangiogenesis and lymphatic remodeling, as well as the crosstalk among LECs, immune cells and cancer cells, which will help to further understand the role of lymphangiogenesis in cancer progression, metastasis, and therapy.