New research has shown that commonly used anti-inflammatory drugs boost immunotherapy cancer treatments.
The proof-of-concept study, carried out by the University of Manchester and the Cancer Research UK Manchester Institute, and funded by Cancer Research UK, has found that anti-inflammatory drugs make tumours more responsive to treatments that boost the anti-cancer function of the immune system.
The study, exploring the use of combination of immunotherapy with widely used anti-inflammatory drugs which are normally used to manage pain and reduce inflammation in diseases like arthritis, has been published in the journal Cancer Discovery.
Improving immunotherapy
The findings have shown that immunotherapy works better and faster in mice when given in combination with anti-inflammatory drugs that target a protein called COX-2. This helps cancer cells escape the immune system and grow aggressively.
The researchers aimed to identify why some tumours are more responsive to immune checkpoint inhibitors than others – a major open question for scientists. Despite this being early research, these findings may have important implications for improving the treatment of lung, intestinal, and breast cancers, among others, which often make a lot of the COX-2 protein.
The researchers treated tumours growing in mice using an immune checkpoint inhibitor, a type of immunotherapy commonly used to treat cancer. They found that less than 30% of the mice responded to treatment – a rate like that seen in some cancer types in human patients – however, when the mice were given the immune checkpoint inhibitors along with a common non-steroidal anti-inflammatory called celecoxib, which targets COX-2 and reduces prostaglandin E2 production, up to 70% of the mice responded to the combined treatment. The team found similar results were achieved when combining immune checkpoint inhibitors with steroids – a finding they say is surprising as steroids are widely considered to suppress the immune system.
The novel approach was conducted in collaboration with the teams of Dr Daniela Thommen and Professor Ton Schumacher from the Netherlands Cancer Institute in Amsterdam.
Dr Santiago Zelenay, from The University of Manchester, said: “These proof-of-concept results are exciting. Our work supports evidence that widely used anti-inflammatory drugs, commonly used to treat conditions like arthritis, can favour a type of inflammatory response that boosts the cancer-restraining function of our immune system.
“These findings inform ongoing and future clinical trials including in Manchester at the Christie NHS Foundation Trust to determine if, and in which cases, these combinations might work best in patients so it’s important to stress that we are not suggesting patients should self-medicate with any of these drugs.”
Immune checkpoints
Immune checkpoint inhibitors block proteins called checkpoints that are made by some types of immune cells, such as T cells. These checkpoints normally stop immune responses from being too strong – which contributes to autoimmune diseases – but tumours can use them to protect themselves from the immune system.
Dr Zelenay said: “Improving the efficacy of the immune checkpoint blockade remains a major clinical need, so our progress in this area is very exciting. Our study has identified mechanisms by which anti-inflammatory drugs can rapidly enhance an immune response in tumours that can prevent their growth.”
Michelle Mitchell, Chief Executive of Cancer Research UK, said: “Checkpoint inhibitors are widely used in the treatment of melanoma and lung cancer to name a few, but they don’t work for everyone. Making them more effective would make a huge difference to many, so finding ways to unleash their potential is vital.
“Although this is early research, funding in this area is important because it can set the course for practice-changing clinical trials later down the line. Repurposing drugs that have already passed safety tests is a great opportunity to save more lives with tools already at our disposal.”
