Gut bacteria influence responses to immunotherapy in mesothelioma patients, study finds

A cancer study has found that certain gut bacteria can influence a patient’s immune system’s ability to fight mesothelioma, an aggressive form of cancer.

Experts believe dietary changes could improve treatment benefits in the future. The study was just published in Nature Communications.

For the past 20 years, Dean Fennell, professor of thoracic oncology at the University of Leicester and a fellow of the Academy of Medical Sciences, has led the development and improvement of mesothelioma treatment.

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

It is a relatively rare but devastating disease. There is currently no cure for mesothelioma, but treatments aim to prolong and improve quality of life.

The aim of this research was to identify personalized treatment pathways for patients with recurrent mesothelioma. Until now, by identifying patients likely to benefit most from different types of drug therapies, cancer genetics has been used to provide insights.

In the most recent paper from Professor Fennell’s MIST trials, the research team evaluated the effectiveness of two immunotherapies, atezolizumab and bevacizumab, in patients with recurrent mesothelioma.

Professor Fennell said: “We found that the immunotherapies we used to treat patients in this study, using immune checkpoint blockade, can provide clinically meaningful control of mesothelioma in a proportion of patients.

“The ecosystem of bacteria that live in each person’s gut has emerged in recent years as an important factor associated with the body’s sensitivity to immunotherapy.

“We wanted to find out how factors, both inside and outside the cancer itself, influenced a patient’s response to immunotherapy.

“So we sequenced the genetic code of the gut bacteria of the patients in this study, to see if there was a relationship with their responsiveness to treatment.”

The study involved 26 patients with recurrent mesothelioma. Their average age was 68 years and they received an average of 4.5 cycles of immunotherapy. The patients’ disease control rate after 12 weeks was assessed.

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

Professor Fennell concludes: “Our work builds on a growing understanding that factors outside the cancer itself, in this case bacteria, which live with us in the gut, may be critical to the success of immunotherapy.

“One of the key findings of our work is that altering the gut microbiome could improve the chances that a patient will benefit from immunotherapy. This could be done, for example, through specific changes in diet, such as increasing fiber intake, which can be implemented by the patient.

“Ongoing work will explore this question, and further evidence will be sought from other MIST trials that have now completed patient recruitment. We look forward to seeing where this research takes us.”

Dr Samantha Walker, Director of Research and Innovation at Asthma + Lung UK, said: “Treatment for mesothelioma has been slow to progress for decades and current treatments do not work particularly well. These findings will bring real hope to the thousands of people affected by mesothelioma. It is truly remarkable to discover that something as simple as the food we eat could have the potential to improve response to immunotherapy.”

“Findings like these demonstrate why funding research is so important. Every five minutes in the UK, someone dies from lung disease. Thousands more live in terror struggling to breathe every day, and yet lung health research is still desperately underfunded. At Asthma + Lung UK, we are fighting for more life-changing and life-saving research to transform the future for everyone living with respiratory conditions.”