N-HCC version 1
Research type
Research Study
Full title
Towards targeting neutrophils in hepatocellular carcinoma
IRAS ID
222658
Contact name
Helen Reeves
Contact email
Sponsor organisation
Newcastle-upon-Tyne Hospitals NHS Foundation Trust
Duration of Study in the UK
4 years, 11 months, 28 days
Research summary
Primary liver cancer – hepatocellular cancer (HCC) - is the 2nd most common cause of cancer death worldwide. HCC is rising sharply in the UK because of a dramatic rise in obesity associated fatty liver disease. Liver cells store fat, which can be associated with an influx of immune cells which damage to surrounding cells and DNA promoting cancer. Treatments options are limited and survival is poor. Dr Reeves team have won a CRUK programme grant to study a particular inflammatory cell - the neutrophil - which they believe is a crucial driver of HCC development and progression. Neutrophils are our first line of defense against infection - engulfing bacteria and releasing factors that recruit other immune cells. This defense mechanism can sometimes damage surrounding tissues. We believe fat in the liver can cause persistent neutrophil activation, making damage more likely. Also, it appears that in the presence of HCC, the neutrophils themselves change, promoting cancer cell survival. The goals for this research programme are to discover how neutrophils promote HCC and influence treatments for HCC, with a view to determining if neutrophil phenotype can be modulated to prevent and treat HCC more effectively.
Briefly, neutrophil phenotyping in HCC patients blood - using flow cytometry, functional assays and expression studies - will be interpreted alongside patient and tumour characteristics, including response to treatment. Mouse models assessing small molecule inhibitors of aspects of neutrophil function will be complemented by lab based human liver tissue and neutrophil studies. This programme aims to establish neutrophils as important cancer modulators, while unlocking new biomarker and therapeutic options for further development.
Approximately 50 patients per year for 5 years will be recruited to this Newcastle based study. It will be observational, based on patient samples and data with no additional procedures. All patients will be considered.
REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
17/NE/0127
Date of REC Opinion
28 Apr 2017
REC opinion
Favourable Opinion