According to a recent study titled “Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade”, published in the Journal of Cancer Research, combined immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade can offer an immediate strategy for overcoming radiation therapy resistance, improving treatment outcomes.
Even though radiotherapy is a successful treatment for different types of cancer, malignant cells that can escape and survive start expressing PD-L1, a protein that, upon interaction with PD1 on the surface of activated lymphocytes, can impair efficient anti-tumoral immune responses.
These immunotherapeutic antibodies work by blocking the contact between receptor and ligand, this way allowing the immune system to target and destroy cancer cells.
Researchers from the University of Manchester’s Cancer Research Centre used different mice models of breast, skin and bowel cancers and exposed them to radiation therapy, immunotherapy, or a combination of the two.
They found that low doses of radiotherapy resulted in the upregulation of PD-L1 ligand on tumor cells.
However, fractionated radiotherapy delivered in combination with anti-PD-1 or anti-PD-L1 monoclonal antibodies was capable of generating an efficient cytotoxic T cell response, improving tumor control, long-term survival, and protection against tumor rechallenge.
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“Using the body’s own defenses to treat cancers has huge potential with early phase clinical trials demonstrating exciting patient benefit, but we are still at the early stages of understanding how best to use these types of treatments,” Dr. Simon Dovedi, from the Manchester Cancer Research Centre, said in a Cancer Research UK press release. “Combining certain immunotherapies with radiotherapy could make them even more effective and we’re now looking to test this in clinical trials to see just how much of a difference it could make.”
Professor Nic Jones, Cancer Research UK’s chief scientist, added “Around half of all cancer patients are given radiotherapy and it has been at the heart of helping improve survival rates so that today one in two cancer patients will survive for at least ten years. Doctors and researchers are constantly looking for ways to improve treatments and this approach could open the door to a whole new way of giving radiotherapy.”
