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Helping the body’s own defences fight cancer cells

23 January 2017

Immunotherapy offers the big hope of teaching the body’s immune system to destroy cancer cells, but there’s a major obstacle: cancer cells can stop immune cells from recognising them as a threat.

When the body detects cancer, it sends immune cells (known as CD8+ Tumour Infiltrating Lymphocytes or TILs) into the tumour to destroy it. However, once inside the tumour, the TILs are suppressed – often by molecules in the tumour that engage inhibitory receptors on the TILs – so that they fail to kill cancer cells. Targeting these inhibitory pathways so that the TILs can function again may lead to the design of new anti-cancer drugs.

Drugs that block two known co-inhibitory receptors, PD-1 and CTLA-4, show great promise in clinical trials. However, they only produce anti-tumour responses in a sub-group of patients and can be associated with severe side effects. Nonetheless, these trials suggest that immunotherapies can give better responses than some chemotherapy and radiotherapy treatments.

Thanks to an EBI Clinical Primer Scheme, Bristol graduate Grace Edmunds, a Research Associate in the School of Cellular and Molecular Medicine, has won a Wellcome Trust Fellowship to take such research forward.

During a one-year science course funded by the Wellcome Trust as part of her intercalated veterinary science degree, Edmunds developed a keen interest in immunology, which formed the theme of her dissertation project and a vacation scholarship funded by the Wellcome Trust.

The EBI Clinical Primer Scheme offers qualified medical, veterinary and dental clinicians the chance to gain firsthand experience of working in a world-class research environment. Edmunds applied to work with Dr David Morgan in Bristol’s Faculty of Biomedical Sciences on a project looking at new ways to restore TIL function.

The research focused on another co-inhibitory receptor, TIM3, which promises greater anti-tumour responses and fewer side effects when targeted for therapy than PD-1 and CTLA-4. Dr Edmunds used genetic engineering techniques to control TIM3 and determine how it might prevent TILs from killing tumour cells. She also looked at what characteristics of the tumour might be causing TIM3 to be present at high levels.

One proposed factor was the accumulation in the tumour of high concentrations of adenosine. Edmunds showed that blocking adenosine receptors on TILs preserved the tumour-killing ability of TILs in mice with cancer. The Wellcome Trust Research Training Fellowship will now allow her to investigate this further.

Further information

See the online case study on the Elizabeth Blackwell Institute for Health Research site.

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