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Bowel cancers adjust themselves to hide from immunotherapies

Published on 15/04/19 at 11:44am

Bowel cancers can avoid being caught by immunotherapy by ‘switching off’ a molecule on the surface of cells that is otherwise recognised by treatment.

A team of researchers found that many mini bowel cancers grown in a lab were able to hide from immunotherapies by reducing levels of the carcinoembryonic antigen (CEA) molecule which immunotherapies use to latch onto in order to attack tumours.

Treatment with the immunotherapy cibisatamab reduced growth by 96 per cent in tumours with high levels of CEA, but by only 20 per cent for low CEA, and 53 per cent in tumours with mixed levels of CEA.

However the researchers found that tumours could alter their levels of CEA after they separated out tumours with high and low levels. They found that the CEA levels had changed in the tumours in both groups.

Study leader Dr Marco Gerlinger, Team Leader in Translational Oncogenomics at The Institute of Cancer Research, London, and Consultant Oncologist at The Royal Marsden, commented: “Cancer is very good at hiding from the body's immune system. The latest successful immunotherapies work by acting as a matchmaker to bring the immune system together with cancer, so that it can see it and attack it.”

“Our study has found that bowel cancers have a way of dodging even the newest of immunotherapies - changing their spots by altering the levels of a key molecule on the surface of cells, so that they become harder to recognise.”

“We used a new technique for growing miniature replicas of tumours to develop a way of testing whether patients will respond to immunotherapy. And best of all, we were able to identify an existing inhibitor of the WNT pathway which could be used to reverse this process. We hope that this could in future help immunotherapies work in more patients, by making cancer cells more visible to immune cells.”

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: “As we move away from one-size-fits-all therapy for cancer, it's so important that we are able to identify which patients are most likely to respond to a drug, and do everything we can to avoid resistance to treatment for as long as possible.”

“This research reveals a way in which cancers are able to hide from a promising new type of immunotherapy. Although the work is still in its early stages, it could be used to develop a test for who is most likely to respond to the drug, and points to possible drug combinations that might prevent or delay resistance.”

Dr Andrew Beggs, a Cancer Research UK expert on bowel cancer, added: “Mini lab-grown tumours have the potential to transform the way we test drugs before clinical trials. From a tiny biopsy, we can recreate the tumour in the lab to better reflect a patient's cancer than with traditional ways of growing cells.”

“This study is an example of creating mini bowel cancer tumours, known as organoids, to guide future research of an experimental immunotherapy. And we can use organoids to learn more about how cancers might respond to drugs, testing many treatments simultaneously to find potential vulnerabilities we might target. Organoid models are increasingly being used in this way to help researchers study, develop and refine possible treatments to test in clinical trials.”

Louis Goss

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