Yellow soft shell D vitamin capsules.
It’s important for everyone to get their daily dose of vitamin D, whether it’s through sunlight or capsules. This essential vitamin is known to help the body absorb calcium, which is the foundation of healthy bones and teeth. According to new research, this nutrient may have unknown benefits in helping the body fight cancer.Preclinical results published in journals science This suggests that vitamin D intake may affect the immune system through the gut. This may improve antitumor responses to a type of cancer immunotherapy called checkpoint inhibitors.
Checkpoint inhibitors and the gut microbiome
At the heart of this research is a vague but increasingly distinct axis between the gut microbiome, the immune system, and cancer.
Over the past 20 years, new connections have been made between the gut microbiome (the trillions of microorganisms that live in our stomachs, intestines, and colons) and the immune system. Researchers note that changes in the microbiome may influence the development and progression of cancers outside the colon, such as breast cancer and liver cancer. The microbiome may also be a key factor in improving checkpoint inhibitors, antibody-based immunotherapies used to treat some types of cancer.
Several strains of intestinal bacteria in mice have been shown to improve antitumor responses to checkpoint inhibitors. Taking antibiotics that damage the gut microbiome also correlates with a decreased response to this inhibitor therapy. Oral supplements can reverse these responses in mice treated with antibiotics. Additionally, studies have observed that melanoma patients who respond to PD-1 checkpoint inhibitors tend to harbor more “good” bacteria. Patients who did not respond had an imbalanced gut flora, which correlated with decreased immune cell activity.
Taken together, these findings suggest a complex interplay between the gut and immune pathways that checkpoint inhibitors affect. Targeting the microbiome through supplements, diet, and other means has the potential to significantly improve outcomes for patients receiving this therapy.
What we know about vitamin D
In their study, researchers at the Francis Crick Institute in London are investigating the link between the gut microbiome and vitamin D-mediated effects on anti-cancer immunity.
Most people are familiar with vitamin D and its effects on bones. Vitamin D, also known as calciferol, is a fat-soluble nutrient that promotes calcium absorption. This nutrient exists in its two forms: vitamin D3 and vitamin D2. The skin can produce vitamin D3 when exposed to ultraviolet B rays found in sunlight. This nutrient is also found naturally in foods of animal origin, including fatty fish such as salmon and tuna. In contrast, vitamin D2 comes from limited plant sources. Both forms are broken down into smaller molecules in the liver and kidneys.
Perhaps the effects of vitamin D on intestinal immunity are less well known. T cells, B cells, and other immune cells in the intestine express vitamin D cell receptors, suggesting a role for vitamin D cell receptors in maintaining intestinal immunity. Vitamin D deficiency is also associated with increased autoimmunity and risk of infections. Does vitamin D interact with intestinal cells and influence antitumor immunity?
New research: microbes and vitamin D in mice
To investigate the link between vitamin D and tumor resistance, researchers Giampasolias and colleagues turned to mouse models of melanoma. The mice were deficient in globulin, a protein that transports vitamin D throughout the body. Animals with less globulin in their blood appear to have higher levels of vitamin D in their tissues. Following this line of thinking, the research team predicted that mice with less globulin, and therefore more vitamin D, would have a better antitumor response.
When challenged with tumors, globulin-deficient mice perform better than globulin-sufficient mice. They have better tumor control, higher intratumoral levels of activated T cells, and respond more readily to checkpoint inhibitor therapy.
The anticancer response of vitamin D appears to be microbiome-dependent. Normal mice should show worse tumor control compared to globulin-deficient mice. However, these mice can develop this tumor resistance if they are housed with globulin-deficient mice for some time. Similarly, fecal transplantation from deficient mice can enhance tumor control in mice with enriched microbiota.
This mechanism appears to be dependent on vitamin D availability. When he fed normal and globulin-deficient mice a diet lacking vitamin D for 4 weeks, both cohorts suffered rapid tumor progression. Conversely, increased vitamin intake increases blood vitamin D levels and reduces tumor growth in normal mice. These levels are comparable to those of globulin deficiency.
In mice without microbiota, feeding a vitamin D-rich diet did not improve antitumor activity, and fecal transplants from vitamin D-deficient mice failed to confer tumor resistance. Both results highlight the link between vitamin D antitumor responses and the microbiome. Gene expression analysis of colon tissue suggests that this interaction acts through vitamin D uptake into intestinal epithelial cells.
Vitamin D and human cancer
The researchers applied their findings to humans. Using data from The Cancer Genome Atlas, they investigated the genetic signature of vitamin D activity in different cancers and found that reduced expression of vitamin D activity correlated with poor patient outcomes. . Additionally, an analysis of more than 1,000 patients treated with checkpoint inhibitors linked reduced tissue vitamin D availability to accelerated cancer progression.
The research team also looked at data on a large cohort of Danish participants who had at least one vitamin D serum measurement before their first cancer diagnosis. They pointed out that decreased serum levels of vitamin D were correlated with increased cancer risk over a 10-year period, emphasizing that vitamin D is a future risk factor for the development of cancer in humans.
Future impact
Checkpoint inhibitors have made remarkable progress in cancer treatment, but have mixed results. In some patients, it may cause long-lasting reactions. For others, there is no reaction at all. More research is needed to elucidate the exact mechanism, but this study points to vitamin D as a possible solution. If this association between nutrients and antitumor responses holds true in humans, cancer patients treated with checkpoint inhibitors could increase their vitamin D intake to improve tumor resistance. It may be possible. This can be a simple dietary change that can make a big difference. This study joins a growing body of research exploring the potential of microorganisms to improve checkpoint inhibitor therapy.
