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Secondary1st is proud to have been able to fund this research project led by Seth Coffelt, Professor of Cancer Immunology at Glasgow University. This report on the project is very detailed but we believe that our supporters will welcome the chance to learn more about the research they have helped to fund.
Immunotherapies are treatments that stimulate the immune system to recognise and fight cancer. The immune system is potentially a very powerful tool for cancer therapies. However, it is very finely tuned, and immune responses that are too strong can also be dangerous. Researchers are learning that in some contexts, and in different tissues, the same molecules and cells can have pro- or anti-tumour effects. Fully understanding these contradictory roles in the immune system is essential for designing successful immunotherapies for breast cancer.
For some cancer types, such as skin and lung cancers, immunotherapies can be very effective. However, current immunotherapy treatments are only effective for a small group of people with breast cancer. Professor Coffelt and his team are working to understand why existing immunotherapies are less effective for breast cancer than other cancer types, and exactly how the immune system might be involved in breast cancer spreading, so that new therapies can be designed to counteract it. They are studying a type of immune cell called gamma delta T cells which reside in tissues such as the lung. These appear to be responsible for creating a hospitable place for breast cancer cells to spread to. An aim of this project is to understand how exactly a molecule called NKG2D affects the behaviour of gamma delta T cells, and how they contribute to secondary breast cancer development. This research could lead to better immunotherapies for breast cancer.
Professor Coffelt and his team have produced a research paper detailing their latest discovery which has been published in the Journal of Experimental Medicine. In this paper the team show how gamma delta T cells can impede some immunotherapies via the IL-17A molecule. They found that two types of immune cells in the lungs, called V gamma and V gamma 4+ gamma delta T cells (Vγ6+ and Vγ4+ γδ T cells), have different responses to cancer. Vγ6+ cells have high levels of a protein called PD-1, while Vγ4+ cells increase production of a protein called TIM-3 when exposed to signals sent from the tumour. They found that blocking PD-1 or TIM-3 increased the numbers of these immune cells, but deleting these immune cells by using genetic techniques improved the effectiveness of certain immunotherapies, suggesting they play a role in resistance to immunotherapy. Overall, the research shows how these different gamma delta T cells are regulated differently during normal conditions and in response to cancer, and how they impact responses to treatment. This finding has revealed a way that might make immunotherapy treatments like pembrolizumab more effective. This could also make these types of treatments suitable for more people in the future.
More recently, Professor Coffelt and his team have been further investigating how delta gamma T cells which produce IL-17 control cancer. They have observed that when they injected breast cancer cells into mice that have had delta gamma T cells genetically deleted, tumours formed in the lung faster compared to normal mice. The team believe that another type of immune cell, Vγ4 cells which can make the molecule IFN-gamma, instead of IL-17, might help control cancer growth. This preliminary research suggests a more complex role for these cells in cancer.
Understanding the way immune cells may help or hinder the spread of breast cancer will help scientists to design effective and safe immunotherapies. Dr Coffelt’s research could eventually lead to new immunotherapy treatments to retrain the immune system to stop breast cancer spreading, instead of helping it.
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Secondary1st is delighted to announce that it has just awarded a grant to a project led by Professor Simak Ali, who is Professor of Molecular Endocrine Oncology at Imperial College London.
Up to 80% of breast cancer diagnoses are ER-positive and many can be treated successfully with hormone therapy. However some ER-positive tumours stop responding after a time and can return, grow and spread. Professor Ali and his team are working to understand how changes in the ER gene help breast cancer cells grow despite hormone therapy. These changes can also help the disease become more aggressive and spread. This is secondary breast cancer and there is currently no cure.
The Charity will be funding a full-time post-doctoral researcher working with laboratory techniques such as epigenomic and transcriptomic profiling, involving the detailed study of changes in cancer cells to produce information on the consequences of these changes. Professor Ali’s team have already found that not all changes in the ER gene affect breast tumour cells in the same way. ER gene changes fall into two groups based on their impact on other genes and the team want to reach a better understanding of the differences between these two groups, leading to new and more effective ways to treat ER-positive secondary breast cancer.
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Dom and Paul are going on a seven-day journey from Essex to the Outer Hebrides and back so that they can cycle the Hebridean Way and raise money for Secondary1st. They will spend four days driving over 1000 miles and ten hours on ferry trips between the islands, with three days to cycle over 150 miles across the islands carrying everything they need on their bikes. They will cycle through some spectacular scenery from white shell beaches to rugged hills of Lewisian gneiss taking two ferries and six causeways to cross between the islands. The Hebridean Way starts from the island of Vatersay at the southern tip of the archipelago and crosses Barra, Eriksay, South Uist, Benbecula, Grimsay, Nort Uist, Berneray and Harris to the Butt of Lewis lighthouse in the far north, a journey of 185 miles or297 km.
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Ruth decided that she wanted to do something different for the weekend. So she climbed the Three Peaks, enjoyed the beautiful scenery and raised money for Secondary1st.
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It seemed a long time ahead when Nolan signed up for it but, after several months of getting up at 5am to train, his cycle ride from Land’s End to John O’Groats is only four weeks away. He will ride through some his favourite places on a journey of over 1,000 miles which will include the equivalent of cycling up Mount Everest twice. From the start at Land’s End his route will take him over Dartmoor, across then Severn Bridge into Wales, through Herefordshire and Shropshire into the Lake District. Then he will cross into Scotland, cycle over the Trossachs, past Loch Lomond, across the Grampians to Inverness and then through the Scottish Highlands to John O’Groats, all in a fortnight.
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Seth Coffelt, who leads the team at the Beatson Institute for Cancer Research at the University of Glasgow which has received funding for the past three years through the generosity of Secondary1st fundraisers and donors, has been appointed Professor of Cancer Immunology at the University of Glasgow. Professor Coffelt and his team have been studying the relationship between cancer and the immune system. Among various healthy cells, immune cells have emerged as powerful instigators of metastasis formation but, at the same time, immune cells can also prevent cancer cells from spreading.
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In 2020 in the middle of the pandemic Angela, who had been diagnosed with secondary breast cancer the previous year, completed the 2.6 challenge by walking for 26 miles on her old cross trainer. Two years later her son John finished the 3 Peaks Challenge to raise money for Secondary1st. This year John has completed the Yorkshire 3 Peaks Challenge with six other people to raise more money for Secondary1st. In total they walked for 24 miles/38.6km, climbed 5200ft/1585m and completed the round trip in 12 hours. The three peaks, Pen-y-Ghent (694 m), Whernside (736m) and Ingleborough (723m), which are part of the Pennine Range, are set in a triangle in the beautiful Yorkshire Dales National Park with the River Ribble between them.
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Just three weeks after finishing in the Brighton Marathon Superhero Tim completed the London Marathon. Marathons, skydiving, fitness challenges… there seems no end to the adventures Tim undertakes to raise money for Secondary1st. He is one of our all-time superheroes.
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A team of scientists at King’s College London has developed an Artificial Intelligence model which analyses immune responses in the lymph nodes to predict the likelihood of developing secondary breast cancer for patients with triple negative breast cancer. Lymph nodes are small bean-shaped structures that are part of the body’s immune system. They filter substances that travel through the lymphatic fluid, and they contain lymphocytes or white blood cells that help the body fight infection and disease. There are hundreds of lymph nodes found throughout the body and they are connected to one another by lymph vessels. Clusters of lymph nodes are found in the neck, axilla (underarm), chest, abdomen, and groin and they are also known as lymph glands. This research which was published in “The Journal of Pathology”, was led by Dr Anita Grigoriadis at the School of Cancer and Pharmaceutical Studies. The AI model was tested on over 5,000 lymph nodes donated to biobanks and there are plans to further test it at other European centres to further increase its precision.
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Last year Nolan rode a zipwire to raise money for Secondary1st. This year he’s planning to undertake a more down to earth challenge. In September he will cycle more than 1000 km, riding all the way from Land’s End to John O’Groats, travelling from one end of the country to the other. He is training hard to prepare for this new adventure.