Gut bacteria may influence immunotherapy success in mesothelioma patients

University of LeicesterSep 5 2024

A cancer study has found that certain gut bacteria may influence whether or not a patient's immune system is successful in fighting mesothelioma, an aggressive form of cancer.

It has led experts to believe that in the future, dietary changes could improve the benefits of treatment. The study has now been published in Nature Communications.

Over the past 20 years, the University of Leicester's Professor of Thoracic Oncology, Dean Fennell, a fellow of the academy of medical sciences, has led on the development and improvements of treatment for mesothelioma. 

Mesothelioma is an aggressive form of cancer which develops in the lining of the lungs or abdomen, and is known to be caused by exposure to the now-outlawed industrial material, asbestos. 

It is a relatively rare disease, but a devastating one. There is no current cure for mesothelioma, with treatments seeking to extend and improve the quality of life.

The focus of this research, funded by the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (BRC) and Asthma + Lung UK has been to identify personalised treatment pathways for patients with relapsed mesothelioma. Thus far by identifying which patients are likely to get the greatest benefit from different types of drug therapies, using the genetics of the cancer to lend insights.

In the most recent paper from Professor Fennell's 'MIST' trials, published in the journal Nature Communications this month, the research team evaluated the effectiveness of two immunotherapies; atezolizumab and bevacizumab, in patients with relapsed mesothelioma. 

We have seen that the immunotherapies we used to treat patients in this study, using immune checkpoint blockade, can achieve clinically meaningful control of mesothelioma in a proportion of patients. 

The ecosystem of bacteria that live in everyone's intestines have emerged in recent years as a significant factor associated with the body's sensitivity to immunotherapy.

We wanted to find out how factors both inside and outside of the cancer per se, were influencing a patient's response to immunotherapy. 

We therefore sequenced the genetic code of the gut bacteria from patients in this study, to establish whether there was a relationship with their responsiveness to treatment." 

Dean Fennell, Professor of Thoracic Oncology, University of Leicester

Twenty six patients with relapsed mesothelioma took part. Their average age was 68 and on average they received 4.5 cycles of immunotherapy. The patient's disease control rate after 12 weeks was assessed. 

The study observed that a positive patient response was more likely if there were more anti-cancer immune cells seen in the mesothelioma. In turn this was associated with the presence or absence of specific gut bacteria; namely Provetella, eubacterium ventriosum group and biophilia.

Professor Fennell concluded: "Our work builds on a growing understanding that factors outside of the cancer per se, in this case bacteria, which live with us in the gut, can be critical to the success of immunotherapy. 

"A key implication of our work is that changing the gut microbiome might improve the odds of patient benefit to immunotherapy. This could be, for example, through specific changes to the diet such as increased fibre intake; something that can be actioned by the patient. 

"Ongoing work will explore this question, with further evidence being sought from other MIST trials that have now completed patient enrolment. We look forward to seeing where this research leads."

Dr Samantha Walker, Director of Research and Innovation at Asthma + Lung UK, said: "With mesothelioma treatment seeing only slow progress for several decades, and current treatments not working particularly well, these results will bring real hope to the thousands of people affected by mesothelioma. It's truly remarkable to discover that something as simple as the food someone eats could have the potential to improve their response to immunotherapy. 

"Results like this demonstrate why it's so important to fund research. Every five minutes in the UK, someone dies from a lung condition. Thousands more live with the terror of struggling to breathe every day – and yet lung health research is still desperately underfunded. At Asthma + Lung UK we're fighting for more life-changing, life-saving research to transform the future for everyone living with breathing problems."

The NIHR Leicester BRC is part of the NIHR and hosted by the University Hospitals of Leicester NHS Trust in partnership with the University of Leicester, Loughborough University and University Hospitals of Northamptonshire NHS Group.