Researchers find way to break tumour ‘walls’

BIRMINGHAM scientists may have found a way to destroy the protective wall that surrounds tumours, potentially re-exposing them to the killing power of the immune system and immunotherapy treatments.

The early findings suggest the approach could help boost the effects of cancer treatments, such as CAR-T therapy, which so far have not been used successfully to tackle solid tumours.

The study was part funded by Cancer Research UK and published in EBioMedicine this week.

Dr Francis Mussai and Dr Carmela De Santo who are based at the University of Birmingham studied immune cells, called myeloidderived suppressor cells or ‘MDSCs’, taken from the blood of 200 adults and children diagnosed with cancer before they had started treatment.

These cells send out chemical signals that shield tumours cells from the immune system and the effects of treatment, and prevent the activation of T cells that can kill tumour cells. When MDSCs are present in higher numbers, the outlook for patients is worse as their cancer can become resistant to treatment.

Researchers showed that an antibody drug that is already available for leukaemia, was able to destroy these immune cells, which protect the solid tumour from the immune system.

Dr Francis Mussai, lead author of the study and Cancer Research UK Clinical Scientist Fellow at the University of Birmingham, said: “Treatments that work with the immune system to kill cancer often fail because it can be difficult for our body’s defences to get access to the tumour cells.

“Our research indicates that giving this antibody drug alongside immunotherapies could dramatically increase the number of patients benefitting from the latest innovations in treatment.”

The researchers also showed that active MDSCs prevented CAR-T cells from working – these are T-cells that have been reprogrammed in the lab to make them more effective at killing cancer cells.

But when they added the antibody drug, it boosted the activity of the CAR-T cells.

“This is the first time we’ve been able to effectively target the immune cells that form a barrier around solid tumours,” added Dr Mussai.

“If this approach works in patients it could improve treatments for many different types of cancer, in both adults and children.

“We envision our approach will have the most impact in CAR-T therapy, which despite showing lots of promise in blood cancer, so far it’s had limited success in solid tumours.”