The Mediterranean Diet: A Promising Ally for Cancer Immunotherapy

Vikas P. Sukhatme, MD, ScD

Introduction

Recent research suggests a compelling connection between dietary habits and response to cancer immunotherapy treatments. Multiple studies now indicate that following a Mediterranean diet rich in whole grains, fish, nuts, fruits, legumes, and vegetables during immune checkpoint inhibitor therapy may significantly improve treatment response and survival outcomes. This emerging research offers a potentially accessible approach to enhancing the effectiveness of these life-saving cancer treatments.

What the Research Shows

A multicenter cohort study by Bolte et al. (2023) involving 91 patients with advanced melanoma from the UK and Netherlands revealed strong evidence about the importance of diet quality. The study examined patients receiving various immune checkpoint blockers (ICBs) such as anti-PD-1 and anti-CTLA-4 therapies.

  • Patients with higher adherence to Mediterranean diet principles showed significantly better response rates to immunotherapy compared to those with lower adherence.
  • Those with the highest Mediterranean diet scores had a 77% probability of overall response to treatment and a 74% probability of progression-free survival at 12 months.
  • The positive association between Mediterranean diet and response remained consistent even after adjusting for factors like age, sex, and body mass index.
  • A cross-validation analysis demonstrated that the Mediterranean diet score could predict progression-free survival and overall response rate with an area under the curve of 0.70.

Similarly important findings on dietary fiber were reported by Spencer et al. (2021) in a study of 128 melanoma patients treated with immunotherapy. Patients consuming sufficient dietary fiber (≥20g/day) showed markedly improved progression-free survival compared to those with insufficient intake. This effect was particularly pronounced in patients who consumed high fiber without probiotic supplements.

The Science Behind Diet's Role

The Mediterranean diet and high-fiber intake appear to influence immunotherapy response through several mechanisms:

  • Modulation of the gut microbiome, promoting beneficial bacteria that produce short-chain fatty acids (SCFAs).
  • SCFAs have immunomodulatory properties that enhance anti-tumor immunity, as demonstrated by Nomura et al. (2020), who found that high fecal SCFA concentrations were associated with longer progression-free survival in patients treated with PD-1 inhibitors.
  • Improvement in the tumor microenvironment, specifically increasing the ratio of beneficial CD8+ cytotoxic T cells to immunosuppressive FOXP3+ regulatory T cells.

Laboratory studies have confirmed these findings. When mice were fed Mediterranean-style or high-fiber diets and treated with anti-PD-1 therapy, they showed delayed tumor growth compared to those on standard or low-fiber diets. Importantly, these effects were not observed in germ-free mice, confirming the gut microbiome's essential role in mediating the diet's benefits.

Clinical Implications

These findings suggest several important considerations for cancer patients receiving immunotherapy:

  • Following a Mediterranean dietary pattern high in vegetables, fruits, whole grains, fish, and nuts may improve treatment outcomes.
  • Ensuring adequate fiber intake (at least 20g per day) could potentially enhance immunotherapy efficacy.
  • Limiting processed foods and red meat aligns with the principles of the Mediterranean diet that appear beneficial.
  • Caution may be warranted with probiotic supplements, as high fiber intake without probiotics showed better outcomes in some studies.

Questions and Considerations

While these findings are promising, several questions remain:

  • The specific components of the Mediterranean diet that most strongly influence immunotherapy response require further investigation.
  • No prospective randomized trials have yet confirmed whether dietary interventions in patients starting immunotherapy improve outcomes.
  • The interplay between diet, the gut microbiome, and immune response is complex and likely involves multiple mechanisms beyond those currently identified.
  • Individual variations in response to dietary interventions need to be better understood to provide personalized recommendations.

What This Means for Patients

If you are receiving immunotherapy for cancer, these studies suggest you might want to discuss dietary choices with your healthcare team. Following a Mediterranean-style diet rich in plant foods and ensuring adequate fiber intake may potentially support your treatment's effectiveness.

This approach represents an accessible way to potentially improve immunotherapy outcomes without new drugs or complex interventions—just adopting dietary patterns that are already widely recommended for general health.

References

  1. 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. 2023;9(5):705-709.
  2. Spencer CN, McQuade JL, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632-1640.
  3. Nomura M, Nagatomo R, Doi K, et al. Association of Short-Chain Fatty Acids in the Gut Microbiome With Clinical Response to Treatment With Nivolumab or Pembrolizumab in Patients With Solid Cancer Tumors. JAMA Netw Open. 2020;3(4).
  4. Zitvogel L, Kroemer G. Boosting the immunotherapy response by nutritional interventions. J Clin Invest. 2022;132(11).