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Why timing matters: How tumours respond to immunotherapy treatments over time

Researchers have identified key differences between cancers that respond to immunotherapy and those that do not.

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Pictured: Dr Melvin Wee Loong Chin and Dr Rachael Zemek

West Australian researchers have identified key differences between cancers that respond to immunotherapy and those that do not, paving the way for more effective treatments for cancer.

The multidisciplinary team, from The Kids Research Institute Australia, The National Centre of Asbestos Related Diseases, The University of Western Australia and The Harry Perkins Institute of Medical Research have published the findings in the journal Nature Communications.

The breakthrough research has the potential to improve cancer immunotherapy, which uses the patient’s own immune system to fight cancer. It is not known why some patients and cancer types respond better to immunotherapy than others.

This is the first study to track what happens after immunotherapy in whole tumours over time and link it to response.

The Kids Research Institute Australia researcher, Dr Rachael Zemek, said the team used lab models to investigate what happens over the course of immunotherapy and what was different between tumours.

We found that a particular immune system pathway was activated when immunotherapy treatment started but was then rapidly shut down in those that responded to therapy.

“This was a surprising finding because we did not expect that shutting down an immune pathway would result in a better immune response. By mimicking this on/off activation, we could dramatically boost the response to immunotherapy treatment,” Dr Zemek said.

The team developed a unique way of analysing cancer samples over the course of treatment and then compared which genes were turned on between responding and non-responding cancers.

“We found that responsive cancers had increased immune activation, however that key pathway was rapidly shut-off,” Dr Zemek said. “The immune system is often seen as something that needs to be constantly “boosted”, therefore treatments are usually given at high doses until they are no longer effective.

Our results challenge this approach and suggest the timing of immune therapies are critically important, even to the point that the exact same target must be turned on and off.

It is hoped that this research could lead to clinical trials within the next couple of years. The Kids Cancer Centre is committed to developing immunotherapy treatments for children, which are less toxic than traditional cancer treatments like radiotherapy and chemotherapy.

Both radiotherapy and chemotherapy can cause life-long side-effects when given in high doses to young children. The research is a collaboration between 16 researchers, involving laboratory scientists, computer scientists and clinicians in Western Australia.

Read the full article here.