Immune cells may be responsible for drug resistance in melanoma patients, according to research published in Cancer Discovery.
Cancer Research UK scientists at The University of Manchester found that chemical signals produced by a type of immune cell, called macrophages, also act as a survival signal for melanoma cells.
When the researchers blocked the macrophages’ ability to make this signal - called TNF alpha - melanoma tumours were much smaller and easier to treat.
When melanoma patients are given chemotherapy or radiotherapy it causes inflammation, increasing the number of macrophages in the body – and raising the levels of TNF alpha. This research suggests that targeting this chemical ‘survival signal’ could lead to new ways to treat the disease.
Dr Claudia Wellbrock, study author and Cancer Research UK scientist at The University of Manchester and member of the Manchester Cancer Research Centre, said: “This discovery shows that immune cells can actually help melanoma cells to survive. Particularly when patients are receiving treatment, the immune cells produce more of the survival signal, which makes treatment less effective. So combining standard treatment with immunotherapy at the same time could potentially provide more long-lasting and effective treatments to increase survival.”
Melanoma is the most deadly form of skin cancer with around 13,300 people diagnosed in the UK each year. Rates of the disease have increased more than fivefold since the mid 1970s.
Professor Richard Marais, director of the Cancer Research UK Manchester Institute and co-author of the study, said: “Melanoma is particularly difficult to treat as many patients develop resistance to standard treatment within a few years. This research provides a key insight into why this is the case.
“Drugs which block this ‘survival signal’ have already been developed and using these along with standard treatment may be a promising new approach for melanoma patients.”
Cancer Research UK joined forces with The Christie NHS Foundation Trust and The University of Manchester to form the Manchester Cancer Research Centre allowing doctors and scientists to work closely together to turn scientific advances into patient benefits sooner.
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Smith et al. The immune-microenvironment confers resistance to MAP kinase pathway inhibitors through macrophage-derived TNFα (2014). Cancer Discovery.
Manchester Cancer Research Centre – www.mcrc.manchester.ac.uk
The Manchester Cancer Research Centre (MCRC) is a partnership founded by The University of Manchester, including the Cancer Research UK Manchester Institute, The Christie NHS Foundation Trust and Cancer Research UK. The MCRC brings together the expertise, ambition and resources of its partner organisations in the fields of cancer treatment and clinical research and provides outstanding facilities where researchers and clinicians can work closely together. The aim of the MCRC is to improve understanding of how cancer develops, in order to translate basic and clinical research into new diagnostic tests and treatments that benefit cancer patients. More information is available at: www.manchester.ac.uk/mcrc
University of Manchester
The University of Manchester, a member of the prestigious Russell Group of British universities, is the largest and most popular university in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. According to the results of the 2008 Research Assessment Exercise, The University of Manchester is one of the country’s major research institutions, rated third in the UK in terms of ‘research power’, and has had no fewer than 25 Nobel laureates either work or study there. The University had an annual income of £807 million in 2011/12.
About The Christie
• The Christie opened in 1901 and is now one of Europe’s leading cancer centres and the largest single-site centre in Europe
• Because of its specialist nature, 26% patients are referred to The Christie from outside the Greater Manchester and Cheshire area
• It has one of the largest radiotherapy departments in the world as well as centres in Oldham and Salford. It also houses the UK’s largest brachytherapy service
• The Christie delivers chemotherapy treatment through the largest chemotherapy unit in the UK, as well as via 10 other sites, its new mobile chemotherapy unit and in patients’ homes
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• Its a charity, which is one of the largest in the UK, provides enhanced services over and above what the NHS funds. It has over 30,000 supporters, who helped raise a record breaking £14.8m last year, with 83p in every pound going directly to patients
• New developments include:
o a new £28.5 million Manchester Cancer Research Centre (MCRC) opening this winter. The MCRC is a partnership between The Christie, The University of Manchester and Cancer Research UK
o a new Maggie’s Centre, expected to open on our site in 2016, providing free practical, emotional and social support for patients, their family, friends and carers
o the UK’s first high energy proton beam therapy service, due to start treating patients in 2018. The Christie was selected to deliver this specialist treatment, along with University College London Hospitals NHS Foundation Trust. Currently patients have to travel to America for this treatment
• The Christie is one of seven partners in the Manchester Academic Health Science Centre, one of only six health science centres in the country
• The Christie’s School of Oncology provides undergraduate education, clinical professional and medical education - the first of its kind in the UK
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• Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
• Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
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• Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years.
• Today, 2 in 4 people survive cancer. Cancer Research UK’s ambition is to accelerate progress so that 3 in 4 people will survive cancer within the next 20 years.
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