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Community blog series: Immune status influences relationship between vitamin D and risk of colorectal cancer

Posted on: January 26, 2015   by  Vitamin D Council


This blog is part of our community-sponsored blog series. Due to their generous support, this individual was able to select a topic meaningful to them and take part in crafting this blog. We thank them and all of our donors for their continued support.

JonathanDr. Jonathan Leibowitz is an internal medicine doctor. Dr. Leibowitz has an immense passion for medical nutrition, which led him to his interest in vitamin D. This interest became an even greater importance to Dr. Leibowitz in 2011, when he was diagnosed with Ewing’s sarcoma.

Ewing’s sarcoma is a cancer that originates in the bone. It is most commonly found in the pelvis, humerus, collar bone, and in Dr. Leibowitz’s case, the femur. He went through a long process of treatment and recovery, which started with chemotherapy. All the meanwhile, Dr. Leibowitz maintained his practice. He cut his estimated recovery time down and now considers himself as fully recovered. Dr. Leibowitz stated, “I am quite happy, I can walk with my kids and be somewhat normal, with a slight limp and some residual pain.  In the end, I view it as having climbed Mount Everest at the cost of a frostbitten toe. As strange as it sounds, when it’s all said and done, despite whatever fear, pain, and misery there was, there is no experience like it.”

In a new study published this past week, researchers from the Dana-Farber Cancer Institute found that people with higher vitamin D levels had high amounts of a type of immune reactivity within their tumor.

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. Healthy 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 healthy 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.

Researchers recently 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, led by Dr. Mingyang Song, 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 4 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.

Between 1989 and 1990 in the NHS and between 1993 and 1995 in the HPFS, blood samples were taken from 32,826 women and 18,225 men.

The researchers used the blood samples to evaluate vitamin D status and only included participants who had levels measured more than 2 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 T cells present in the tumors.

They took this a step further and quantified the amount of different types of T cells including CD3+, CD8+, CD45RO+ and FOXP3+ cells.

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.

Did the number of T cells influence the preventive effect of CRC associated with high vitamin D status?

Here’s what the researchers found:

  • Vitamin D status was not associated with risk of overall CRC (p for trend = 0.09).
  • 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 (p < 0.001).
  • High vitamin D levels were not associated with reduced risk of CRC in which the tumors had mild or no T cell count (p = 0.55).
  • Within the group with the highest vitamin D levels, those with a high amount of CD3+ cells but not with low amounts of CD3+ cells had a lower risk of colorectal tumors (p = 0.006).
  • There was no association between vitamin D and other subtypes of T cells on 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.

They concluded,

“We found that the relationship between plasma 25(OH)D and risk of CRC differed by intratumoral periglandular 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.”

They went on to state,

“Our data provide evidence for a possible role of tumor stromal immune cells in generating bioactive 1,25(OH)2D3 to augment the influence of vitamin D on neoplastic and non-neoplastic cells in an autocrine and paracrine fashion.”

In discussing the limitations of the study, the researchers note that the inclusion of only patients with available tumor tissue data may lead to selection bias. Additionally, 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.


Song, M. et al. Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status. Gut, 2015.

2 Responses to Community blog series: Immune status influences relationship between vitamin D and risk of colorectal cancer

  1. Rebecca Oshiro

    A lovely blog! Thank you for sharing your story with our community, we appreciate it.

  2. IAW

    Yes, thanks so much!!!!

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