Our immunity system It is one of our greatest allies in suppressing the development of cancer in our body, but it often needs a little push. One of the ways to do this is using a class of drugs called checkpoint inhibitors. These medicines unlock certain immune cells – called killer T cells — who try to kill cancer cells. They can be a very effective treatment for certain skin, lung and kidney cancersbut unfortunately do not work in all patients.
A series of studies published in 2018 demonstrated that the microbiome of patients may be related to the results. People who do or do not respond to checkpoint inhibitor therapy have differences in the bacteria generally present in the intestine. In 2021, two studies found that transferring microbes from fecal matter from people who reacted to bowel therapy for those who they didn’t react it could enhance therapeutic benefits in these last patients.
Now, an unexpected finding in mouse studies published in the April 25th issue of the journal Sciencesuggests another factor that could explain why people react differently to cancer therapy: vitamin D level in intestinal tissue it can promote the presence and growth of certain bacteria that stimulate T cells to attack cancer.
Vitamin D, which we can obtain through our diet – consuming foods such as fatty fish or egg yolk – or producing through skin exposure to Sun light, plays an essential role in our metabolism and the health of our bones, muscles, nerves and immune system. There was also evidence that it could play a protective role in cancerbut even so, the new findings in mice came as a surprise.
Testing whether the same mechanisms work in humans will require more and careful studies, he says. Caetano Reis e Sousaan immunologist at the Francis Crick Institute in London, England, and senior author of the study, but it is a hypothesis that deserves investigation.
“Vitamin D has an impact on the activity of hundreds of genes, so it is complex,” says Reis e Sousa. However, in several sets of dates analyzed by Reis e Sousa and his colleagues, patients with higher vitamin D activity demonstrated greater chances of surviving various cancers and responded better to immunotherapy.
The researchers also found evidence that in Denmark, where sunlight that helps humans produce vitamin D through the skin is relatively rare, detailed health records reveal that people with vitamin D deficiency had a high risk of develop cancer over the next decade. “It’s probably an underestimation,” says Reis e Sousa, “because at least some of these people must have decided to take vitamin D supplements after discovering this deficiency.
This study provides yet another reason to make sure you produce or consume enough vitamin D, says Carsten Carlberg, a biochemist at the Polish Academy of Sciences in Olsztyn, who has studied the vitamin’s impacts for decades and was not involved in the vitamin D study. Science. However, he warns that it is It is unwise to jump to conclusions about humans based on discoveries in mice. “Seventy-five million years separate us from rats.”
An intriguing observation
Reis e Sousa has long been interested in genes that affect the ability of the immune system to attack cancer cells. To identify these genes, researchers in his laboratory work with mice in which a gene they suspect is involved in promoting or suppressing cancer has been deactivated. By transplanting cancer cells into these modified mice, they can track the time it takes for the cells to develop a tumor.
When his colleague Evangelos Giampazolias, now at the Cancer Research UK Manchester Institute, discovered that disabling the gene that gives the instructions for making vitamin D-binding protein reduced the growth of cancer cells in mice, Reis e Sousa was intrigued. But it was the next experience, he says, “that really caught my attention”. To ensure that the findings were not due to some peculiarity of the laboratory environment, Reis and Sousa’s team created mice with the gene deactivated in the same cage as mice that had a fully functional version. To your surprise, cagemates’ tumors also grew more slowly. Why would the proximity of an animal that is more resistant to cancer slow the growth of a tumor in normal mice?
The power of feces
Giampazolias and Reis e Sousa didn’t take long to remember that mice eat each other’s feces and that something in these feces must have been transferred from the mice with the deactivated gene to the normal mice with which they shared the cage – and that was a possible explanation for what happened.
To test whether the effect had anything to do with the gut microbes living in the genetically modified mice, Reis and Sousa’s team administered antibiotics to mice with activated genes. When this made their resistance to cancer disappear, as well as their ability to transmit it to their cage mates, it became clear that the intestinal bacteria in the mice’s feces were somehow slowing tumor growth. Vitamin D-binding protein maintains most of the vitamin D in the blood, explains Reis e Sousa. “This reduces the amount of vitamin D that reaches tissues, including those lining the intestine.”
The higher levels of vitamin D achieved by deactivating the gene encoding the vitamin D-binding protein promoted the growth and presence of a specific bacteria, thefragilis, also common in the human colon. And this bacteria, explains Reis e Sousa, can stimulate the immune system.
Deactivate the gene, increase the amount of vitamin D in the diet of genetically modified mice or add more Bacteroides fragilis to the intestine of rats had the same effect: the existence of more T cells attacking the tumor and slowing its growth. Due to these higher levels of vitamin D, the mice also demonstrated a better reaction to immunotherapy. “We still don’t know how bacteria do this,” says Reis e Sousa. “But the effect is unquestionable.”
New therapies
Reis e Sousa, who is of Portuguese origin and whose darker complexion means he produces less vitamin D in a sunny London, discovered he was lacking the vitamin about a decade ago and has been taking a supplement ever since. “As a general rule,” he says, “if we are diagnosed with a vitamin D deficiency, it seems sensible to try to correct it. But that doesn’t depend on this study, obviously.”
He adds that people should always consult your family doctor before taking vitamin supplements – even if they know they are vitamin D deficient – until the impact of vitamin D supplements on cancer risk and other aspects of human health is better known. “There could be negative effects that we haven’t yet discovered, such as an increase in autoimmune diseases.” The researcher also does not advise people to spend too much time in the sun in spring to synthesize vitamin D. “We do not recommend increasing sun exposure, which can also increase the risk of skin cancer, nullifying any effect. You don’t need to sunbathe to get vitamin D. Taking a walk should be enough.”
More importantly, say Reis and Sousa, the study could inspire further investigation into whether vitamin D or vitamin D supplements Bacteroides fragilis may improve outcomes for cancer patients receiving immunotherapy or other treatments.
Walter Willett, a physician and nutritional researcher at Harvard’s TH Chan School of Public Health who was not involved in this study agrees that the data from Reis and Sousa’s new study suggests Potential benefits of vitamin D in human cancer patients. “This is consistent with some of our own findings. We found out lower risks of colorectal cancer in women with higher vitamin D levelsin the blood. I was also involved in a clinical trial that demonstrated a decrease in cancer mortality in people taking vitamin D supplements.”
Willett thinks vitamin D supplements are probably a good idea. “It makes sense that most people living in northern climates take vitamin D supplements and don’t bother testing their vitamin D levels. The best way to do this is with a multivitamin/multimineral supplement that contains 800 or 1,000 international doses of vitamin D, which costs less than 10 cents per day.
It remains to be confirmed whether the benefits of vitamin D in humans are mediated by the microbiome, adds Willett. “This will require new and larger studies, carried out over several years.”
Many doctors are currently explore ifit will be beneficial to manipulate the microbiome to improve cancer therapy, says Reis e Sousa. “It could be incredibly successful in improving therapeutic outcomes. But it can also be dangerous, especially when people are immunocompromised. We hope that our discoveries can lead to more refined therapeutic applications.”
