The relationship between vitamin D, immune system and cancer

Jonathan S. Leibowitz, PhD, Maimonides Medical Center, Internal Medicine, Brooklyn, New York, USA

“The immune system plays an independent role in the tumor fight by finding and killing cancer cells. This, however, is where some of the biggest obstacles to immune therapy are, as tumors are experts in disguise and hide quite well from the body’s immune system, thus making it hard for the immune system to even recognize a tumor as foreign, by itself. Vitamin D has a complex and very important relationship with the human immune system. Adequate levels of vitamin D help strengthen the immune system and ensure that immune cells are communicating and functioning properly. Research also suggests that certain immune cells have the ability to locally activate and convert 25(OH)D into the active form of vitamin D, 1,25(OH)D. Together, this evidence suggests that sufficient circulating levels of 25(OH)D helps the immune system to function and, in turn, a properly functioning immune system can activate and use vitamin D to help fight off pathogens.

It is no surprise then that both vitamin D and the immune system are associated with the development of cancer. Research shows that vitamin D can bind to cancer cells and instruct them to die or stop growing. One important type of immune cell is a T cell. T cells are a class of lymphocytes, or white blood cell, that are mainly involved in activating an inflammatory response in order to fight off invading bacteria, pathogens or tumor cells. In cases of colorectal cancer (CRC), for example, T cells are able to get inside a tumor and activate an immune response. The number of T cells a person’s immune system produces can indicate their ability to fight off the tumor and thus overall CRC prognosis.

In a new study, researchers found that people with higher vitamin D levels had high amounts of a type of immune reactivity within their CRC tumor (1). They hypothesized that the association between vitamin D status and risk of CRC might be influenced by the number of T cells present in a CRC tumor. The research team looked at data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). The NHS began in 1976 and recruited 121,701 female nurses while the HPFS began in 1986 and recruited 51,529 male professionals. Both studies involved a food frequency questionnaire every four years and a separate questionnaire every two years to collect updates on medical, lifestyle and other health-related information. The medical questionnaires given every two years included questions regarding any diagnosis of colon or rectal cancers. In total, 318 men and women diagnosed with CRC met the necessary study requirements. These CRC cases were matched with a total of 624 healthy individuals to serve as a control group. The researchers used the blood samples to evaluate vitamin D status and only included participants who had levels measured more than two years before CRC diagnosis. These participants were then grouped into three groups depending on their vitamin D status. Additionally, only participants with CRC tissue samples were included. The researchers used these samples to evaluate the amount of different types of T cells present in the tumors.

The study results showed that the participants’ vitamin D status was not significantly associated with risk of overall CRC. Within the group with the highest vitamin D levels, those with the highest amount of T cells in their tumors had a significant 90% reduced risk of CRC compared to those with the lowest amount of T cells. High vitamin D levels were not associated with reduced risk of CRC in which the tumors had mild or no T cell count. Within the group with the highest vitamin D levels, those with a high amount of the T cell type CD3+ but not with low amounts of CD3+ cells had a lower risk of colorectal tumors. The researchers conducted a separate analysis to determine if degree of inflammation affected the relationships observed and found that it did not change their results.

The scientists concluded that the relationship between plasma 25(OH)D and risk of CRC differed by intratumoral immune reaction to CRC; high 25(OH)D was associated with lower risk of tumors possessing high-level lymphocytic reaction, but not with tumors having low-level or no lymphocytic reaction. In discussing the limitations of the study, the researchers noted that the observational design of the study means other confounding variables may exist and that causation cannot be determined. Further research is needed to confirm these findings and expand knowledge on the relationship between vitamin D, immune function, and CRC.”

Based on: Leibowitz J. S. Immune status influences relationship between vitamin D and risk of colorectal cancer. Vitamin D Council. Community Blog. Published online January 2015.