Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functio
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PRECLINICAL STUDIES
Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells Jie Hu 1 & Enxin Wang 1 & Lei Liu 1 & Qiuhe Wang 1 & Dongdong Xia 1 & Wei Bai 1 & Jun Tie 1 & Xiaomei Li 1 & Jie Yuan 1 & Shuya Yang 2 & Dongbo Jiang 2 & Jingqi Shi 2 & Yuanjie Sun 2 & Jing Wang 2 & Chunmei Zhang 2 & Jing Niu 1 & Kai Li 1 & Chuangye He 1 & Wengang Guo 1 & Yong Lv 1 & Hui Chen 1 & Xulong Yuan 1 & Tianlei Yu 1 & Zhengyu Wang 1 & Bohan Luo 1 & Na Han 1 & Ying Zhu 1 & Zhanxin Yin 1 & Daiming Fan 3 & Zhuoli Zhang 4 & Kun Yang 2 & Guohong Han 1 Received: 4 November 2019 / Accepted: 2 December 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
Summary 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. Keywords Hepatocellular carcinoma . Sorafenib . NK cell . Subset . Clinical outcome
Abbreviations NK cell Natural killer cell
* Kun Yang [email protected] * Guohong Han [email protected] 1
Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
2
Department of Immunology, Fourth Military Medical University, Xi’an, China
3
State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
4
Department of Radiology, Northwestern University, Chicago, IL, USA
HCC VEGFR PDGFR-β TAM IFN-γ HCV mRECIST OS AASLD BCLC ECOG HIV AEs CT CR PR SD
HEPATOCELLULAR carcinoma Vascular endothelial growth factor receptor Platelet-derived growth factor receptor β Tumor-associated macroph
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