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Gene signature discovery may predict response to immune therapy

November 08, 2018

(TORONTO, Canada, Nov. 8, 2018) - Scientists led by Dr. Daniel De Carvalho at Princess Margaret Cancer Centre have discovered a gene signature biomarker that may predict which patients will respond - or not - to immune therapy.

The findings are published online today in Nature Communications (doi: 10.1038/s41467-018-06654-8).

Dr. De Carvalho, principal investigator, says the gene signature relates to the body's molecular network called the extracellular matrix (ECM) that underpins and physically supports cells. For cancer patients with the gene signature, the research suggests the ECM can stiffen around the diseased cells to form a barrier that immune cells simply cannot penetrate.

"The ECM gene signature associated with response to immune therapy is important because as of today we do not have a very good way to predict which patient will respond or which patient will not respond," says Dr. De Carvalho, Senior Scientist at the cancer centre, University Health Network.

The multi-institutional scientific team used a big data approach and examined available data across thousands of patient samples from many different cancers to find that in some patients the immune cells were not penetrating the tumour, despite the fact these patients had molecular markers that would predict immune response.

"That's when we started to think that ECM could be playing a role in actually physically blocking the immune system."

With further experimental study to validate the biomarker, Dr. De Carvalho says the research lays the foundation for a new therapeutic strategy to focus first on ways to disable the ECM to enable immunotherapy.

"The ultimate goal is to find a biomarker that can help the clinician decide if a patient should receive immunotherapy or not. For those who will not respond, the answer could be the patient would first receive a drug to target the ECM, and then be able to respond to immune therapy."
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Dr. De Carvalho is a trained immunologist (University of Sao Paulo, Brazil) with postdoctoral training in cancer epigenomics (University of Southern California, USA) whose research focuses on cancer epigenetics. He holds the Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy and is an Associate Professor in Cancer Epigenetics, Department of Medical Biophysics, University of Toronto.

The research was funded by The Princess Margaret Cancer Foundation, the Cancer Research Society, the Canadian Cancer Society, the Ontario Institute for Cancer Research, a Canada Research Chair and the Canadian Institutes of Health Research.

About Princess Margaret Cancer Centre, University Health Network

The Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital, Toronto Rehabilitation Institute and the Michener Institute for Education; all affiliated with the University of Toronto. For more information, go to http://www.theprincessmargaret.ca or http://www.uhn.ca .

University Health Network

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