CCL2、CCL7、ICAM-1 和 VCAM-1 在内皮细胞与 NK 细胞相互作用中的作用

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- and IL-1 , which were produced by tumor-associated CD11b + cells, which included F4/80 + macrophages. TNF- -treated endothelial cells increased NK cell migration by producing CCL2 and CCL7, which was proved by transwell and imaging assays. TNF- -treated endothelial cells adhered well to NK cells, which was due to a TNF- -induced increase in ICAM-1 and VCAM-1 expression on endothelial cells.

Imaging data confirmed that TNF- -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.