Diet may determine who responds to cancer immunotherapy

Why a cancer treatment works well for one patient and far less well for another has long puzzled doctors, and new research suggests that what people eat may be part of the answer.

Researchers at McGill University in Canada found that certain diets normally associated with weight gain improved the effect of a widely used form of immunotherapy in mice, a result that may help explain a pattern scientists have noticed in cancer patients for years.

Some patients with a higher body mass index (BMI) appear to respond better to treatments that help the immune system attack cancer, even though obesity is generally linked to higher cancer rates and deaths.

Researchers call this contradiction the “obesity paradox”, SciTechDaily reports.

The new findings suggest that body weight itself may not be the key, and that the explanation could lie in food, gut bacteria and the way the two interact with the immune system.

The treatment studied is known as an immune checkpoint inhibitor. The immune system has built-in brakes that stop immune cells attacking too aggressively, and cancers can exploit those brakes to avoid destruction.

Checkpoint inhibitors block those signals, giving immune cells a better chance of recognising and attacking tumour cells. The drugs work remarkably well for some patients but give others much less benefit, which has pushed researchers to look beyond the tumour for factors that influence success.

The team was co-led by Daniela Quail, an associate professor in McGill's department of physiology and principal investigator at the Rosalind & Morris Goodman Cancer Institute. Other senior members were McGill's Logan Walsh and Bertrand Routy and Arielle Elkrief of CR-CHUM, according to McGill. The research, published in Nature under the title Diet–microbiome synergy underlies obesity-associated immunotherapy efficacy, was led on the laboratory side by McGill PhD graduate Lysanne Desharnais with Quail.

The researchers tested 12 diets in mice and found that some diets associated with obesity improved the animals' responses to checkpoint inhibitors. The benefit appeared even after shorter periods on those diets, making it harder to explain through long-term weight gain alone.

That pointed the researchers to the gut microbiome, the trillions of microorganisms in the digestive system. These bacteria depend partly on nutrients that reach them through food, so changing the diet can change which microbes thrive and how they behave, with consequences that can extend to the immune system.

Quail said the bacteria in the gut and the food people eat have a synergistic relationship, and that even with the right bacteria, the foods that nourish them can determine whether a patient responds to treatment.

The finding complicates the idea that having certain beneficial gut bacteria is enough to improve a treatment response. What those bacteria are fed may matter too, and the same bacteria may not have the same effects under different diets. That interaction could help explain why a higher BMI has sometimes been linked to better responses: rather than excess weight directly helping the treatment, some of the biological changes produced by particular diets may alter gut microbes in ways that affect the immune response.

Quail said the findings were surprising because they showed a benefit from some obesogenic diets, and that the relationship between diet and cancer treatment is more complex than a simple message to eat well and exercise.

The work was carried out in mice and has not been tested in patients. The authors do not advocate long-term obesogenic diets because of their well-established health risks, OncoDaily reported. The researchers now hope to find out what is driving the effect on the gut microbiome and to harness it to improve treatment.

Sources: SciTech Daily, McGill University & OncoDaily