Finding improves tumour response to immunotherapies

Researchers from The University of Western Australia and Olivia Newton-John Cancer Research Institute have found a new way to improve treatment of tumours that previously did not respond to immunotherapies.

“By combining inhibition of Hck with immunotherapy, the growth of cancers poorly responsive to immunotherapy alone was significantly reduced.”

Associate Professor Fiona Pixley, UWA

Immunotherapy is a treatment that uses certain parts of a person’s immune system to fight diseases such as cancer. It can be done in a number of ways and involves stimulating, or boosting, the natural defences of the immune system so that it works harder or smarter to find and attack cancer cells.

Associate Professor Fiona Pixley and Jay Steer, from UWA’s School of Biomedical Sciences, were co-authors of Therapeutic inhibition of the SRC-kinase HCK facilitates “T cell” tumor infiltration and improves response to immunotherapy published in Science Advances.

They discovered that isolating a particular molecule found in certain immune cells that hadn’t traditionally responded well to immunotherapy could turn things round, which may ultimately lead to better responses to immunotherapies for patients with a range of cancers.

“Cancer immunotherapy has revolutionised the treatment of several cancers, such as melanoma, in the past decade but some cancers do not respond to these new therapies,” Associate Professor Pixley, Head of Pharmacology and Toxicology at UWA, said.

“Non-responding tumours are typically ‘immunologically cold’ as they contain few of the immune cells called T cells that are targeted by these immunotherapies.”

The non-responding tumours contain different immune cells, known as macrophages and dendritic cells, which are immunosuppressive and stop immunotherapy from working.

Researchers found inhibiting a molecule called Hck, only found in macrophages and dendritic cells, changed their behaviour and enabled a powerful immune response to immunotherapies.

“By combining inhibition of Hck with immunotherapy, the growth of cancers poorly responsive to immunotherapy alone was significantly reduced,” Associate Professor Pixley said.

The study found stimulating immune cell activation, while inhibiting the immunosuppressive micro-environment, enhanced T-cell infiltration, resulting in reduced tumour growth.

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