Gut bacteria may influence response to cancer immunotherapy

Cancer Research UK

The type of bacteria in the gut of patients with advanced melanoma may influence their response to a certain type immunotherapy, according to new research.

A US study, carried out at The University of Texas and published in Science, suggests that looking at the communities of bacteria in the gut – called the microbiome –  might help predict which melanoma patients would respond to a type of immunotherapy called anti-PD-1 therapy.

The team gathered stool samples from 89 patients with advanced melanoma that had spread and who were about to start taking an anti-PD-1 immunotherapy drug.  

Six months after taking the first dose, the team grouped patients based on those whose tumours had responded to the drug and those who did not. They then compared the types of bacteria present in the samples taken before treatment in these groups. 

"You can change your microbiome, it's really not that difficult, so we think these findings open up huge new opportunities." - Prof Jennifer Wargo, study leader.

Those who responded to treatment had a more diverse community of bacteria in their gut than those whose cancer worsened after treatment.

Patients who had a more diverse population of bacteria in the gut also had their disease controlled by the immunotherapy drug for longer, compared to those who had less diversity in their gut bacteria.

"You can change your microbiome, it's really not that difficult, so we think these findings open up huge new opportunities," said Professor Jennifer Wargo, who led the study.

The team also found that having more of a few certain types of bacteria in the gut was also beneficial.

In particular, patients who specifically had a lot of bacteria from the family Faecalibacterium had a longer length of time where their disease did not get any worse, compared to those who had low amounts.

Dr Emma Smith, from Cancer Research UK, said: “It’s fascinating to see that the type of bacteria living in a patient’s gut could be a sign of whether they are likely to benefit from immunotherapies.”

The team then altered the microbiome of mice with melanoma by transplanting into them stool samples from patients who did and did not respond to immunotherapy treatment. The mice who received a transplant from patients who responded to treatment had an improved response to anti PD-1 drugs.

Dr James Kinross, a microbiome expert from Imperial College London, said: “What this study demonstrates is that you can’t have personalised healthcare without understanding how the bacteria in our gut influences the medicines we take." 

“We already know that gut bacteria can cause certain side effects in some cancer treatments, but this study builds on previous work and shows that you can change how drugs work by modifying the bacteria in the gut."

Kinross also said that this part of the research was done in mice with melanoma who have different communities of bacteria in their gut. They also don’t go through the same complex "cancer journey" that humans go through.

"Before gut bacteria changes the way we treat cancer we need to understand how it changes through a human’s cancer journey,” he adds.

“These studies are quite remarkable and have immediate clinical implications." - Dr Alastair Watson, Cancer Research UK

A second study, also published in Science, adds to the evidence that gut bacteria may influence the effectiveness of immunotherapy drugs.

The study looked at whether taking antibiotics affected the overall survival of patients with either non-small cell lung cancer or urothelial carcinoma who were treated with anti-PD-1 drugs.

Out of 249 patients, 69 had been prescribed antibiotics while on or just before starting treatment.

These patients had infections that needed treating.

On average the overall survival of those who had taken antibiotics was lower compared to those who did not have them.

Dr Alastair Watson, a Cancer Research UK-funded microbiome expert, who called both studies "quite remarkable", said they could also have "immediate clinical implications".

“They strongly suggest that antibiotics should be used with great caution in patients receiving immunotherapy as they may kill off gut bacteria that are important for enhancing anti-tumour immune responses.”

Wargo said that a lot more work is needed to fully understand the relationship between the types of gut bacteria and response to immunotherapy treatment.

“One of the big challenges for using immunotherapies to treat cancer is understanding which patients will respond, and this research is a step towards helping doctors to identify these people,” said Smith.

References

Gopalakrishnan, V. et al. (2017) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science DOI: 10.1126/science.aan4236

Routy, B. et al. (2017) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumours. Science DOI: 10.1126/science.aan3706