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New Study Suggests Diet May Affect Response To Cancer Immunotherapy Drugs

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People with a type of skin cancer who consumed a high-fiber diet responded better to immunotherapy treatment than those with poorer diets, according to data presented at a media preview of the American Association for Cancer Research (AACR) annual meeting.

Melanoma is a type of skin cancer which although very treatable if caught early, still kills approximately 9,000 Americans a year, mainly people who are diagnosed a more advanced stage of disease where the cancer has spread to other parts of the body.

Immunotherapy drugs such as those targeting PD-1/PD-L1 or CTLA-4  as well as T-VEC, the first ever viral therapy for cancer treatment to be FDA-approved, have had a remarkable impact on the survival from advanced melanoma. A study in 2001 calculated the chance of surviving 10 years after diagnosis to be under 10%, but now largely thanks to these immunotherapy agents, the survival rate has soared to over 50%.

However, some patients don't respond to immunotherapy at all and although researchers have started uncovering evidence as to why this might be, with recent research suggesting tumors with more DNA mutations are more likely to respond, it is likely to not be one single reason but a combination of factors.

Last week a further study suggested that people with melanoma are less likely to survive if they are or have ever been smokers, with the researchers suggesting that suppression of the immune system was likely responsible for this disparity. Now new research due to be presented at AACR has indicated that diet may be vitally important in determining whether melanoma patients respond to immunotherapies.

“We found that diet and supplements appear to have an effect on a patient’s ability to respond to cancer immunotherapy, most likely due to changes in their gut microbiome,” said Christine Spencer, PhD, research scientist at the Parker Institute for Cancer Immunotherapy.

The researchers collected fecal samples from 113 melanoma patients starting immunotherapy treatment at MD Anderson Cancer Center. They looked at the types of bacterial species found in the patients' gut microbiome and found that a higher microbiome diversity was correlated with a better response to immunotherapy after controlling for differences based on age, sex and body mass index (BMI).

“In our current study, we wanted to look at how diet and supplements affect the microbiome and modulate responses to checkpoint immunotherapy,” said Spencer.

Previous work by Spencer and colleagues from MD Anderson reported that patients with a diverse gut microbiome with lots of bacteria called Ruminococcaceae were more likely to respond to anti-PD-1 drugs.

Patients in the recent study had to complete dietary surveys of their eating habits, with the researchers finding that patients who ate whole grains, fruits and vegetables and an overall high-fiber diet had gut bacteria which were associated with a good response to immunotherapy. Those with diets high in added sugars and processed meat were less likely to see the immunotherapy work for them. In a subset of 46 patients treated with anti-PD-1 drugs, patients who had a high-fiber diet were five times as likely to respond to the immunotherapy than those with a low-fiber diet.

“We know from prior research that eating a higher-fiber diet has a lot of health benefits. But with this preliminary research on cancer patients and the microbiome, it appears that fiber is also linked to a better response to immunotherapy,” said Spencer.

This of course raises the tantalizing possibility something as simple as modulation of diet or even a transplant of gut bacteria associated with a favorable response to immunotherapy could be used to make more cancer patients respond to immunotherapy.

“The gut microbiome plays a big role in moderating the immune system, so the idea that we could potentially change the microbiome—whether by diet or other means—to improve response to immunotherapy treatment is really exciting,” said Spencer.

More than 40 percent of cancer patients surveyed reported that they regularly used probiotic supplements, which were associated with lower diversity in the gut microbiome. This lower diversity was in-turn associated with a poorer response to immunotherapy.

“Based on these preliminary results, we need to reconsider use of over-the-counter probiotics in patients with cancer, at least until we have more data supporting their potential safety and efficacy,” said senior author Jennifer Wargo, MD, Professor of surgical oncology and genomic medicine at MD Anderson.

This isn't the first time that the safety of probiotic supplements, which are not FDA-regulated, have been called into question. Last year two studies from the Weizmann Institute of Science in Israel suggested that probiotics had no effect on the gut microbiome in most people and perhaps more worryingly, could actually be harmful if taken after antibiotics.

However, the research linking immunotherapy response in cancer patients to microbiome composition and dietary habits is still preliminary, with the researchers stressing that larger studies are needed before modulating diet can be considered for melanoma patients on immunotherapy treatment.

According to an article published in The Lancet earlier this month there are, however, 39 clinical trials currently ongoing which are modulating the gut microbiome in cancer, including three involving immunotherapy agents. One of these, run by the University of Pittsburgh intends to perform a fecal matter transplant from people who do respond to anti-PD-1 drug pembrolizumab into those who are resistant to see if it makes them respond to the drug.

This intervention is certainly a little dramatic for those who do not have cancer nor need immunotherapy treatment currently, but in the meantime, increasing your fiber intake is always a good idea and is associated with several health benefits, including a lower risk of some cancers.