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The project, co-led by Dr Robert Köchl from King's College London, aims to uncover how fluid and mechanical stress created in the tumour environment can limit the immune system's capacity to fight cancer, and could pave the way for the development of new treatment strategies.
T cells under pressure
T cells are a type of white blood cell that play a crucial role in the immune response by identifying and destroying infected or abnormal cells, including cancer cells. A group of T cells called cytotoxic T cells (CTLs) are responsible for directly seeking out and attaching to tumour cells to kill them, making them a key focus in cancer immunotherapy research.
The new research programme (titled "T cells under pressure") will explore how the physical properties of tumours help them evade destruction by the immune system. Tumours are 'stiffer' and more densely packed than healthy tissues, in part due to the build-up of cancer cells and fluids. The team hypothesises that these tumour characteristics make it harder for CTLs to penetrate and move through the tumour's environment to get to the cancer cells.
'Our initial research suggests that both the increase in fluid and mechanical pressure within tumours makes it difficult for CTLs to penetrate them, reducing the ability of CTLs to kill and eliminate cancer cells,' said Dr Robert Köchl, Senior Lecturer in the School of Immunology & Microbial Sciences at King's.
'With this study, we want to understand how pressure inside tumours affects the signals that control T cell movement and function – so we can find ways to boost their ability to squeeze in, stay active, and kill cancer cells,' said Robert.
Using animal models of breast cancer and melanoma, human breast cancer samples and advanced imaging techniques, the team will investigate how these pressures impair the ability of CTLs to perform their immune function. The findings could reveal new ways to overcome these physical barriers to improve cancer treatments.
Professor Marco Fritzsche, Professor of Biophysical Immunology at the Kennedy Institute of Rheumatology, University of Oxford said: 'I am very pleased to now be able to study how tumours adapt their mechanics to evade the human immune system, which may help to identify new therapeutic strategies for patients.'
Research Information Manager at Cancer Research UK, Dr Dani Edmunds, said: 'Cancer is a master at disguising itself from the immune system. We need to keep finding better ways for the immune system to recognise cancer and stop it in its tracks.
'This research is looking at high pressure inside tumours, and how it can make it too tight a squeeze for our immune cells to get in. Finding new ways for the immune system to get into the tumour will help us devise kinder, more targeted treatments, so that more people can live longer, better lives, free from the fear of cancer.'
The project is due to start in July 2025.