Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 113, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.109332
Keywords
NK cell; Endothelial cell; Cell-cell interaction; Chemokine; Adhesion molecule
Categories
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT)
- [2017R1A5A2015541]
- [2020R1A2C2004200]
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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.
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.
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