January 25, 2022

Fiber in diet linked to cancer immunotherapy response

At a Glance

  • People who ate a high-fiber diet and didn’t use over-the-counter probiotic supplements lived the longest after immunotherapy for melanoma.
  • The findings, which were confirmed in mouse studies, suggest that microbes in the gut can be modified to improve this type of cancer treatment.
Metastatic melanoma cells Melanoma cells with podosomes (yellow), actin-rich structures than enable cancer cells to move and spread. Cell nuclei (blue), actin (red), and an actin regulator (green) are also shown. Julio C. Valencia, NCI Center for Cancer Research

Immunotherapies, which stimulate the immune system to help the body fight cancer, have shown substantial promise for the treatment of many tumor types. These include melanoma, a potentially deadly type of skin cancer.

But while tumors shrink or even disappear in some people given immunotherapy, others have no response at all. Researchers have been trying to understand the factors that affect individual responses to immunotherapy.

The microbes found in the gut, called the gut microbiome, have emerged as one such factor. Gut microbes are thought to play a role in the body’s immune response. Early studies found that modifying the gut microbiome may improve the odds of tumor response to immunotherapy.

Researchers led by Dr. Giorgio Trinchieri of NIH’s National Cancer Institute (NCI) and Drs. Carrie Daniel and Jennifer Wargo from the University of Texas M.D. Anderson Cancer Center examined the links between diet, gut microbes, and response to immunotherapy in 128 people with melanoma.

The participants reported their eating patterns and any use of probiotic supplements in the month before receiving immunotherapy. The team also took stool samples to analyze participants’ gut microbiomes. Results were published on December 24, 2021, in Science.

People who reported higher fiber intake, which promotes healthy gut microbes, had better responses to treatment overall. After adjusting for other factors, the researchers found that every 5-gram increase in daily fiber intake corresponded to a 30% lower risk of cancer progression or death.

Overall, people who ate the most fiber and didn’t use probiotics had the best responses to immunotherapy. Probiotics didn’t appear to improve survival. In fact, the data suggested they might lower survival.

The team studied mice to confirm these findings. Mice with melanoma tumors were treated with immunotherapy. Those fed a high-fiber diet had slower tumor growth than those fed a fiber-poor diet. Mice fed the high-fiber diet also had more anticancer immune cells in their tumors. In contrast, diet didn’t affect tumor growth in mice without any gut bacteria.

The team also found that mice given probiotics had a reduced response to immunotherapy and developed larger tumors than control mice.

“Many factors can affect the ability of a patient with melanoma to respond to immunotherapy,” Trinchieri says. “However, from these data, the microbiota seems to be one of the dominant factors. The data also suggest that it’s probably better for people with cancer receiving immunotherapy not to use commercially available probiotics.”

Larger studies including people with other cancer types are needed to more fully understand the relationship between diet, microbes, and immunotherapy. A clinical trial is now testing the effect of diet on the gut microbiome and immunotherapy outcomes in people with melanoma.

Related Links

References: Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, Khan MAW, Zhang X, White MG, Peterson CB, Wong MC, Morad G, Rodgers T, Badger JH, Helmink BA, Andrews MC, Rodrigues RR, Morgun A, Kim YS, Roszik J, Hoffman KL, Zheng J, Zhou Y, Medik YB, Kahn LM, Johnson S, Hudgens CW, Wani K, Gaudreau PO, Harris AL, Jamal MA, Baruch EN, Perez-Guijarro E, Day CP, Merlino G, Pazdrak B, Lochmann BS, Szczepaniak-Sloane RA, Arora R, Anderson J, Zobniw CM, Posada E, Sirmans E, Simon J, Haydu LE, Burton EM, Wang L, Dang M, Clise-Dwyer K, Schneider S, Chapman T, Anang NAS, Duncan S, Toker J, Malke JC, Glitza IC, Amaria RN, Tawbi HA, Diab A, Wong MK, Patel SP, Woodman SE, Davies MA, Ross MI, Gershenwald JE, Lee JE, Hwu P, Jensen V, Samuels Y, Straussman R, Ajami NJ, Nelson KC, Nezi L, Petrosino JF, Futreal PA, Lazar AJ, Hu J, Jenq RR, Tetzlaff MT, Yan Y, Garrett WS, Huttenhower C, Sharma P, Watowich SS, Allison JP, Cohen L, Trinchieri G, Daniel CR, Wargo JA. Science. 2021 Dec 24;374(6575):1632-1640. doi: 10.1126/science.aaz7015. Epub 2021 Dec 23. PMID: 34941392.

Funding: NIH’s National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), and National Heart, Lung, and Blood Institute (NHLBI); US-Israel Binational Science Foundation; Melanoma Research Alliance; American Association for Cancer Research; Andrew Sabin Family Fellows Program; MD Anderson Cancer Center; U.S. Department of Defense; American Society of Clinical Oncology; Elkins Foundation; Seerave Foundation; Rising Tide Foundation; Mark Foundation; Longenbaugh-Torian Fund; Cancer Research Institute; Cancer Prevention and Research Institute of Texas; U.S. Department of State; Fulbright Franco–Américaine Commission; National Health and Medical Research Council of Australia; Charles A. King Trust; John M. Skibber Endowed Professorship; Michael and Patricia Melanoma Research Endowment; Richard E. Haynes Distinguished Professor in Clinical Cancer Prevention; American Cancer Society, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; AIM at Melanoma Foundation; Cancer Fighters of Houston; Anne and John Mendelsohn Chair for Cancer Research.