Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56^dimCD16⁺ NK cells increased after two months of treatment, while the percentage of CD56^brightCD16⁻ NK cells decreased, leading to a dramatically reduced ratio of CD56^bright and CD56^dim NK cells (ratio^bri/dim). Patients with low ratio^bri/dim exhibited better mRECIST responses and longer median OS than those with high ratio^bri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56^brightCD16⁻ and CD56^dimCD16⁺ NK cells, which was associated with the outcomes including OS of HCC patients.