Problem addressed, background and strategic significance

Colorectal cancer claims 44 lives daily in the UK. Our own immune system is capable of killing cancer cells but often, our immune cells are ‘blocked’. Immunotherapy is a new and effective type of treatment that removes the brakes stopping our immune system. Patients who respond well to immunotherapy survive longer and effects are sustainable. Moreover, immunotherapy has revolutionised outcomes in skin and lung cancer. Sadly these successes have not been mirrored in colorectal cancer and the mechanisms by which colorectal cancer cells elude our immune cells remain to be identified. Previous research has suggested that patients who responded better have colorectal cancer with ‘microsatellite instability’ (MSI). However, not everyone with MSI colorectal cancer respond to immunotherapy. We plan to investigate why some patients respond to immunotherapy while others do not by examining the type and functional status of immune cells in MSI colorectal cancer.

Method(s) used

We will collect blood sample and colorectal tissue from patients during surgery. We will extract immune cells from collected tissue and compare the type of immune cells present in the tumour and blood to find unique immune ‘fingerprint’ to individual colorectal cancer. The pattern of these ‘fingerprints’ can help us identify which patient will be resistant to immunotherapy.

Hoped for results of this research

We want to identify biomarkers that could help identify patients that will benefit from immunotherapy. We also hope to find out why some patients do not respond to immunotherapy and methods to overcome this.

What this research is expected to add to the knowledge of bowel disease and what is the impact you hope to achieve for patients?

The identification of these subsets of immune cells can be used as immune biomarkers to select MSI colorectal cancer patients who are susceptible or resistant to immunotherapy, helping to not only direct the personalisation of highly expensive immunotherapy agents, but also to help identify new approaches in immunotherapy.