‘When good cells turn bad’ – immune cells can promote liver cancer

In a paper published in the journal Nature Communications, the team describes how cells called neutrophils can promote cancer-inducing effects in liver cells that are already damaged due to chronic disease.

It is already known that chronic liver inflammation or hepatitis are risk factors for developing a particular type of liver cancer known as hepatocellular carcinoma (HCC). However, inflammation is a complicated process involving many different types of cells from our immune system working together. This has made it difficult to determine the molecular links between inflammation and HCC.

This latest research identified neutrophils as a key inflammatory cell type that drives the progression of liver damage to cancer in mice. The team at Newcastle University’s Institute of Cellular Medicine – Derek Mann, Professor of Hepatology, Dr Fiona Oakley and Dr Caroline Wilson – showed that among the effects that neutrophils produce, is an increase in Reactive Oxygen Species (ROS), part of normal cell metabolism which at low levels helps the body’s immune system but which can cause damage to cellular components, including damage to DNA, if they reach high levels.

Professor Mann explains: “Neutrophils normally help our bodies to fight infections by producing powerful substances that kill germs. They are also sent to our liver when it is damaged by substances like alcohol, only in this scenario, when the liver is being subjected to sustained damage on an ongoing basis, there is a continuous flow of neutrophils to the damaged site. This overwhelming response, and the flood of germ-killing molecules the neutrophils release, can actually harm the genetic material in liver cells and stimulate cancer growth.”

The research, which was jointly funded by the European Commission, Medical Research Council and the Wellcome Trust, also suggested a possible way towards stopping the cancer-promoting actions of neutrophils.  Dr Oakley added: “We found that neutrophils cause an increase in ROS in liver cells and this damages their DNA which can be a trigger for cancer growth. Remarkably, anti-oxidants were able to almost completely stop HCC in our experiments”

Dr Mann commented: “Now we know that neutrophils are the culprits we can move forward with new studies aimed at stopping their cancer-promoting activities in high risk patients suffering from severe liver disease. We need to develop our understanding of how we might be able to prevent ongoing neutrophil traffic to the liver, or block the release of ROS. We also need to carry out more work to understand how we might be able to use anti-oxidants, naturally found in fruits and vegetables.”

Liver cancer is a devastating disease with a poor prognosis and limited therapeutic options.  The World Health Organisation estimate that liver cancer was the second leading cause of cancer deaths in 2012, accounting for almost 750,000 deaths worldwide. 

The article, ‘NFΚB1 is a suppressor of Neutrophil Driven Hepatocellular Carcinoma’ is published on 16 April 2015 in Nature Communications.

Pictured: A Haematoxylin and Eosin stained human liver with liver cancer, shown at 600x magnification. The arrows point to neutrophils.


Key Facts:

  • Newcastle University is a Russell Group University
  • Ranked in the top 1% of universities in the world (QS World University Rankings 2014)
  • Ranked 16th in the UK for global research power (REF 2014)
  • Ranked 10th overall in the UK and 3rd for quality of staff/lecturers in the Times Higher Education Student Experience Survey 2015
  • Amongst our peers Newcastle is:
    • Joint 6th in the UK for student satisfaction
    • Ranked 1st in the UK for Computing Science research impact, 3rd in the UK for Civil Engineering research power and 11th in the UK for Mathematical Sciences research (REF 2014)
    • Ranked 8th in the UK for Medical and Life Sciences research quality (REF 2014)
    • Ranked 3rd in the UK for English, and in the top 12 for Geography, Architecture and Planning, and Cultural and Media Studies research quality (REF 2014)
    • Engineering and Physical Sciences Research Council (EPSRC) top 20 strategic partner
  • 93.7% of our students are in a job or further training within six months of graduating
  • We have a world-class reputation for research excellence and are spearheading three major societal challenges that have a significant impact on global society. These themes are: Ageing, Sustainability, and Social Renewal
  • Newcastle University is the first UK university to establish a fully owned international branch campus for medicine at its NUMed Campus in Malaysia which opened in 2011
  • Our international students put Newcastle University in the world’s top 50 (ISB 2013) of global universities.
  • Newcastle University Business School is one of 20 Triple Accredited Business Schools in the UK
Categories Cancers