Fig. 3. The effects of tumor-associated lymphatic endothelium on antitumor immunity.
The lymphatic vessels (green) guide antigens and DCs to lymph nodes to facilitate the DC–T cell interaction to prime T cells (only if the LN microenvironment allows this to be productive). Notably, lymphatic vessels are more common peritumorally, while intratumoral vessels are prone to collapse. Moreover, defects in contractile events for lymph flow impair drainage. Thus tumor drainage, albeit physically hampered in a tumor, is required for developing antitumor immunity. Importantly, additional LEC features (intrinsic or tumor induced) counteract the induction of an adaptive immune response. This is exemplified by the increased PD-L1 expression and protolerogenic cell surface protein composition (co-inhibitory over co-stimulatory factors). Drainage of immunosuppressive immune cell types (e.g., MDSCs, immature DCs) influence the LN microenvironment to favor immunosuppressive populations (e.g., Treg and MDSCs) that facilitate lymphovascular premetastatic niche formation. Moreover, reduced CCL-21 levels in dLNs diminish the opportunity for DCs and naive T cells to interact and impairs T-cell retention for efficient expansion before LN egress.