Effect of secretory DKK3 on circulating CD56bright natural killer cells in patients with liver cancer

Abstract

Background: Liver cancer seriously threatens human health. Natural killer (NK) cells are an important part of the innate immune system and have strong anti-tumor ability. Immunotherapy based on NK cells has become a hot topic in the treatment of liver cancer.

Methods: In this study, we checked the serum DKK3 (sDKK3) and circulating CD56^bright NK cells using ELISA and flow cytometry, respectively, in the blood of liver cancer patients. The effect on recombinant human DKK3 (rhDKK3) on CD56^bright NK cells was analyzed in vitro.

Results: We found low levels of sDKK3 in liver cancer patients and a negative correlation between sDKK3 and circulating CD56^bright NK cells. In addition, we found that DKK3 induced the differentiation and improved the cytotoxicity of CD56^bright NK cells for the first time. It could be used as an agonist for NK cell-based immunotherapy.

Conclusions: Improving the clinical efficacy of NK cells through DKK3 will become a new strategy for cancer immunotherapy.

Keywords: DKK3; Liver cancer; NK cells; cytotoxicity; differentiation.