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Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells
- Source :
- Investigational New Drugs. 38:1247-1256
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.
- Subjects :
- Adult
Male
0301 basic medicine
Sorafenib
Carcinoma, Hepatocellular
Adolescent
Antineoplastic Agents
Kaplan-Meier Estimate
Young Adult
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Immunologic Factors
Pharmacology (medical)
Protein Kinase Inhibitors
Response Evaluation Criteria in Solid Tumors
Aged
Proportional Hazards Models
Aged, 80 and over
Pharmacology
biology
business.industry
Liver Neoplasms
Middle Aged
medicine.disease
Phenotype
Peripheral blood
Peripheral
Killer Cells, Natural
Granzyme B
030104 developmental biology
Oncology
Perforin
030220 oncology & carcinogenesis
Hepatocellular carcinoma
biology.protein
Cancer research
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15730646 and 01676997
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Investigational New Drugs
- Accession number :
- edsair.doi.dedup.....21a008b9757eaac46e387932044ae2b5