Figure 2.

Naïve T cell homing in tumors. Similar to effector T cells, naïve T cells require multiple signals to extravasate through the vasculature. Contrastingly, naïve T cells require specialized vasculature called high-endothelial venules (HEV), which are capable of expressing the proper receptors and chemokines. Tethering and rolling is initiated by peripheral node addressin (PNAd) binding to CD62L on the T cell. Chemokines CCL19 and CCL21 activate lymphocyte function-associated antigen-1 (LFA1) integrin, and facilitate firm adhesion and arrest by binding of activated LFA1 to intracellular adhesion molecule 1 (ICAM-1). PNAd, CCL19, and CCL21 get upregulated by factors expressed in the tissue microenvironment, LTα₃ induces PNAd expression through TNFR signaling, and interferon ((IFN)γ induces CCL19 and CCL21 expression. Tumor cells can inhibit expression of these cytokines, as well as directly downregulate ICAM-1 expression through endothelin-1-endothelin receptor B (ET_BR) signaling. Made with Biorender.com.