Immunomodulatory properties of the lymphatic endothelium in the tumor microenvironment

Abstract

The tumor microenvironment (TME) is an intricate complex and dynamic structure composed of various cell types, including tumor, stromal and immune cells. Within this complex network, lymphatic endothelial cells (LECs) play a crucial role in regulating immune responses and influencing tumor progression and metastatic dissemination to lymph node and distant organs. Interestingly, LECs possess unique immunomodulatory properties that can either promote or inhibit anti-tumor immune responses. In fact, tumor-associated lymphangiogenesis can facilitate tumor cell dissemination and metastasis supporting immunoevasion, but also, different molecular mechanisms involved in LEC-mediated anti-tumor immunity have been already described. In this context, the crosstalk between cancer cells, LECs and immune cells and how this communication can shape the immune landscape in the TME is gaining increased interest in recent years. In this review, we present a comprehensive and updated report about the immunomodulatory properties of the lymphatic endothelium within the TME, with special focus on primary tumors and tumor-draining lymph nodes. Furthermore, we outline emerging research investigating the potential therapeutic strategies targeting the lymphatic endothelium to enhance anti-tumor immune responses. Understanding the intricate mechanisms involved in LEC-mediated immune modulation in the TME opens up new possibilities for the development of innovative approaches to fight cancer.

Advances in lymphatic metastasis of non-small cell lung cancer

“…In recent years, immunotherapy has brought wish to patients with advanced NSCLC, while the immunotherapy effect of different populations seems to be different, and the expression of programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) is the main drug reference index in clinical practice [ 19 ]. As an important component of TME, lymphatic system functions an important role in regulating immune response [ 20 ].We summarized some interesting genes, which regulated lymphatic metastasis of NSCLC, exerted synergistic role in immunotherapy at the same time. They seems to have great potential to be used as prognostic indicators for evaluating immunotherapy and synergistic therapeutic targets just like tumor anti-angiogenesis therapy [ 21 , 22 ].…”