Mediterranean Diet Associated with a Higher Probability of Response in Patients with Advanced Melanoma Treated with Immune Checkpoint Blockade

A cohort study conducted among patients with advanced melanoma from the UK and the Netherlands suggests that a Mediterranean-style diet that is enriched in whole grains, fish, nuts, fruit, legumes and vegetables is associated with a higher probability of response to immune checkpoint blockade. The results suggest that the Mediterranean dietary pattern is associated with a higher probability of progression-free survival (PFS) and overall response rate (ORR) in patients receiving immune checkpoint blockade for advanced melanoma and a potential role for diet in improving treatment outcomes. Further studies in different countries are needed to confirm the findings and offer patient-specific advice. The findings are published by Dr. Rinse K. Weersma of the Department of Gastroenterology and Hepatology, University of Groningen and University Medical Centre Groningen in Groningen, the Netherlands and colleagues on 16 February 2023 in the JAMA Oncology.

Many patients do not tolerate and/or respond to immune checkpoint blockade. Recent evidence suggests that variability in the efficacy of immune checkpoint blockade is partially explained by differences in the gut microbiome. The abundance of several gut bacteria predictive of response to immune checkpoint blockade is associated with diet.  While evidence supporting the immunomodulatory and antitumour activities of specific nutrients is increasing, studies that comprehensively assess the association of overall diet composition with response to immune checkpoint blockade are still lacking.

In this study, we aim to investigate associations between different dietary patterns and ICB response and immune-related adverse events (irAEs) using a multinational prospective cohort of patients with advanced melanoma.

The multicentre cohort study (the PRIMM study) was conducted in cancer centres in the Netherlands and UK and included 91 patients with advanced melanoma who were treatment naïve for immune checkpoint inhibitors and receiving immune checkpoint blockade between 2018 and 2021. The aim was to investigate associations between different dietary patterns and immune checkpoint blockade response and immune-related adverse events (irAEs). Patients were treated with anti-PD1 and anti-CTLA4 monotherapy or combination therapy. Dietary intake was assessed through food frequency questionnaires before treatment. Clinical endpoints were defined as ORR, PFS at 12 months (PFS-12), and irAEs that were grade 2 or higher.

There were a total of 44 participants from the Netherlands with mean age of 59.43 years of whom 22 were women (50%) and 47 participants from UK with mean age of 66.21 years of whom 15 were women (32%). Dietary and clinical data were prospectively collected. Logistic generalised additive models revealed positive linear associations between a Mediterranean dietary pattern and the probability of ORR and PFS-12 (probability of 0.77 for ORR; p = 0.02; false discovery rate, 0.032; effective degrees of freedom, 0.83; probability of 0.74 for PFS-12; p = 0.01; false discovery rate, 0.021; effective degrees of freedom, 1.54).

This cohort study found a positive association between a Mediterranean diet, a widely recommended model of healthy eating, and response to treatment with immune checkpoint blockade. The traditional principles of the Mediterranean diet remain the most widely used dietary recommendations of public health institutions globally. A potential mechanism underlying the association between diet and immunotherapy response is the gut microbiome. Preclinical studies have shown immunomodulatory and antitumour activities of several nutrients, including fiber, polyphenols, and antioxidants, that are mediated via the gut microbiome. The Mediterranean diet has been associated with an increased abundance of bacteria producing short-chain fatty acids that have been shown to be predictive of immunotherapy response in several studies.

The authors commented that specific food preferences and nutrient sources vary across geographies, suggesting a need for multinational cohort studies paired with more resolution on food compositions.

This work was supported by the Seerave Foundation. It was also supported by the Dutch Cancer Society grant.


Bolte LA, Lee KA, Björk JR, et al. Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma. JAMA Oncol. Published online 16 February 2023. doi:10.1001/jamaoncol.2022.7753