Fig. 1.

Factors affecting CD8+ T cell trafficking and localization. CD8+ T cells in the peripheral blood are recruited or trafficked locally into the TME in response to the binding of various secreted chemokines (CCL3, CXCL9, CXCL10, CXCL11, CCL4, CCL5, CCL20, and CXCL16) and their corresponding receptors expressed on tumor cells and stromal cells of the TME. CD8+ T cell trafficking is positively influenced by the interaction between adhesion molecules (ICAM-1, VCAM-1) expressed by endothelial cells and their corresponding receptors which are expressed on the surface of CD8+ T cells. The successful binding of the chemokine ligand fractalkine and CX3CR1 facilitates CD8+ T cell trafficking. The interaction between sphingosine-1-phosphate (S1P) and its corresponding receptors importantly facilitate CD8+ T cell trafficking. The above mentioned receptor-ligand interactions are marked with a solid line and arrow because they promote CD8 T cell trafficking. The binding of endothelin-1 to ET_B, its corresponding receptor on endothelial cells, reduces ICAM-1 expression, thus preventing T cell adhesion and subsequently preventing CD8+ T cell trafficking. The chemokine-chemokine receptor interaction between CCL2 and CCR2 inhibits CD8+ T cell trafficking. The later mentioned interactions between endothelin-1 and ET_B as well as CCL2 and CCR2 are marked as dotted lines because their interactions inhibit CD8+ T cell trafficking.