High-fibre diet improves response to immunotherapy in melanoma patients

According to a new study by the University of Texas MD Anderson Cancer Centre, melanoma patients who ate more fibre during immunotherapy, survived longer without cancer growth.

The findings of the study were published in the journal Science.

The benefit was most noticeable in patients who did not take commercially available probiotic supplements. Parallel pre-clinical studies supported the observational findings.

"Research from our team and others has shown that gut microbes impact response to immunotherapy treatment, but the role of diet and probiotic supplements have not been well studied," said co-senior author Jennifer Wargo, MD, professor of Genomic Medicine and Surgical Oncology.

"Our study sheds light on the potential effects of a patient's diet and supplement use when starting treatment with immune checkpoint blockade. These results provide further support for clinical trials to modulate the microbiome with the goal of improving cancer outcomes using dietary and other strategies."

Patients who reported eating more fruits, vegetables, legumes and whole grains met the study threshold for sufficient fibre intake. The 37 patients with sufficient fibre intake had improved progression-free survival (median not reached) compared to the 91 patients with insufficient fibre intake (median 13 months). Every five-gram increase of daily fibre intake was associated with a 30 per cent lower risk of cancer progression or death.

When the patients were further grouped according to high- or low-fibre diet and commercially-available probiotic supplement use, response to immunotherapy was seen in 18 of 22 patients (82 per cent) who reported both sufficient fibre intake and no probiotic use, compared to the response seen in 60 of 101 (59 per cent) patients who either reported insufficient fibre intake or probiotic use. The response was defined as complete or partial complete or partial tumour shrinkage or stable disease for at least six months. Probiotic use alone was not associated with a significant difference in progression-free survival or odds of response to immunotherapy.

"Dietary fibre is important for gut health, just as it's important for overall health, and the two things are very tightly intertwined," said co-senior author Carrie Daniel-MacDougall, PhD, associate professor of Epidemiology.

"In this study, we saw that dietary fibre also may be important to cancer treatment, which brings us to a point where we can design interventional studies to answer the questions that patients really want to be answered: 'Does what I eat now matter and could it impact my treatment outcome?' We're united in working to find answers for our patients," she added.

Differences in gut micro biota and pre-clinical models

The study began with analysing the gut micro biome profiles of 438 melanoma patients, 321 of whom had the late-stage disease and were treated with systemic therapy, and 293 of whom had an evaluable response to treatment over follow-up. The majority of these patients (87 per cent) received immune checkpoint blockade, most commonly PD-1 inhibitors. A total of 158 patients also completed a lifestyle survey of antibiotics and probiotics usage; of these, 128 completed a dietary questionnaire as they began immune checkpoint therapy.

The research team reinforced their prior findings, which showed a higher abundance of Ruminococcaceae and Faecalibacterium prausnitzii, well-known and potentially beneficial bacteria involved in the digestion of fibre or starch - in patients who responded to immunotherapy. In contrast to the previous findings, the overall diversity of gut bacteria was not associated with response to immunotherapy, potentially due to the larger size of this patient cohort.

The researchers also tested higher versus lower fibre diets and probiotic use in several preclinical melanoma models to shed light on the potential mechanisms behind the observational findings from the patient cohorts. In multiple models, probiotic use was associated with impaired response to immune checkpoint blockade, larger tumours, lower gut micro biome diversity and less cytotoxic T cells in the tumour microenvironment. A high-fibre diet was associated with slower tumour growth and a significantly higher frequency of CD4+ T cells in pre-clinical models treated with PD-1 inhibitors.