The role of CCL2, CCL7, ICAM-1, and VCAM-1 in interaction of endothelial cells and natural killer cells

Natural killer (NK) cell-based therapy has been studied for the treatment of patients with cancers, but the inadequate infiltration of NK cells into solid tumors remains a big challenge to its clinical application. In this study, we examined the interaction between NK cells and endothelial cells, which might play a major role in NK cell homing to solid tumors. We found that endothelial cells were activated by TNF-alpha and IL-1 beta, which were produced by tumor-associated CD11b+ cells, which included F4/80+ macrophages. TNF-alpha-treated endothelial cells increased NK cell migration by producing CCL2 and CCL7, which was proved by transwell and imaging assays. TNF-alpha-treated endothelial cells adhered well to NK cells, which was due to a TNF-alpha-induced increase in ICAM-1 and VCAM-1 expression on endothelial cells. Imaging data confirmed that TNF-alpha-treated endothelial cells transfected with ICAM-1 or VCAM-1 siRNAs did not establish stable contacts with NK cells. Taken together, our data suggest that CCL2, CCL7, ICAM-1, and VCAM-1 expressed by endothelial cells will be potential targets to guide adequate interaction with NK cells, which is a crucial step for NK cell homing to the tumor microenvironment.

Automated summary

This study examined the role of endothelial cells in the homing of natural killer (NK) cells to solid tumors. It was found that TNF-α and IL-1β activated endothelial cells, which increased NK cell migration and adhesion to the endothelial cells through the production of CCL2 and CCL7, as well as the upregulation of ICAM-1 and VCAM-1 expression on the endothelial cells.