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Invest New Drugs. 2019 Dec 13. doi: 10.1007/s10637-019-00885-2. [Epub ahead of print]

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

Author information

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.
5
Department of Immunology, Fourth Military Medical University, Xi'an, China. yangkunkun@fmmu.edu.cn.
6
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. hangh@fmmu.edu.cn.

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.

KEYWORDS:

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

PMID:
31832851
DOI:
10.1007/s10637-019-00885-2

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