Fig. 4

Complex T-cell chemotaxis of tumor-associated endothelial cells. (Figure created with BioRender.com). Tumor-associated endothelial cells (TECs) reduce immunostimulatory capacity by downregulating the expression of genes involved in antigen presentation (MHC class I and II), immune cell homing (ICAM1), and chemotaxis (CCL2, CCL18, IL-6). This downregulation may be associated with the downregulation of Fos/Jun and ELF3. Additionally, TECs expressing high levels of ACKR1 may inhibit T cells recruitment and infiltration by reducing circulating chemokine concentrations. TECs may also lead to T cell incompetence or induce regulatory T cell formation through high levels of expression of genes for MHC-II-mediated antigen presentation and processing, along with low expression of co-stimulatory molecules such as CD80 and CD86. They can also inhibit T cell activity through PDL2-PD-1 interactions or upregulate the expression of FasL, leading to the killing of T cells through Fas-mediated apoptosis. TECs infiltrating and excluding tumors can recruit CX3CR1 tumor-associated macrophages