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

Jie Hu, Enxin Wang, Lei Liu, Qiuhe Wang, Dongdong Xia, Wei Bai, Jun Tie, Xiaomei Li, Jie Yuan, Shuya Yang, Dongbo Jiang, Jingqi Shi, Yuanjie Sun, Jing Wang, Chunmei Zhang, Jing Niu, Kai Li, Chuangye He, Wengang Guo, Yong LvHui Chen, Xulong Yuan, Tianlei Yu, Zhengyu Wang, Bohan Luo, Na Han, Ying Zhu, Zhanxin Yin, Daiming Fan, Zhuoli Zhang, Kun Yang, Guohong Han*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16 NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/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 CD56brightCD16 and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

Original languageEnglish (US)
Pages (from-to)1247-1256
Number of pages10
JournalInvestigational New Drugs
Volume38
Issue number5
DOIs
StatePublished - Oct 1 2020

Keywords

  • Clinical outcome
  • Hepatocellular carcinoma
  • NK cell
  • Sorafenib
  • Subset

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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