Can Vitamin D Increase the Long-Term Effectiveness of Immunotherapy in Cancer Treatment?

The immune system is a barrier to cancer formation. Cancer cells spreading from their origin do not always produce metastases, because immune cells (T cells) recognize and kill most while they travel through blood and lymph. Cells escaping immunity through mechanisms such as activating its brakes or mutating to avoid recognition spread and settle in new organs. Strengthening immunity and reactivating this defense therefore became a treatment goal. Immunotherapy developed from this idea makes immunity more effective and attacks cancer cells more strongly, aiming to prevent multiplication and spread and sometimes eliminate them entirely.

Immunotherapy can be applied in different ways, including monoclonal antibodies. After CTLA-4, a molecule on important immune cells called T cells, was found to brake their activity, monoclonal antibody drugs began to be developed. The principle is administering laboratory-produced antibodies that block immune-braking molecules such as CTLA-4. After CTLA-4, new brakes called PD-1 and PDL-1 were identified. Recently developed drugs ipilimumab, nivolumab and pembrolizumab have attracted great attention by working in many cancers.

Other examples include interferons and interleukins. Interferons are synthetic proteins produced in laboratories to strengthen immunity. Interleukins are cytokines released from leukocytes and mediating interactions among these white blood cells. Cytokines play important roles in orderly immune function. Cancer vaccines are another method, stimulating the body's defenses to recognize and destroy particular cancers.

Although these treatments shrink or eliminate tumors, researchers continue studying how immunity recognizes and attacks cancer cells upon recurrence and how recurrence can be prevented. With this in mind, a study published in Immunity considered the body's need for immunological memory. Researchers believed immunity had several ways to achieve this. By preventing it from braking itself, they sent many T cells, which kill harmful foreign substances, to attack cancer cells. Although more T cells kill more cancer cells, researchers saw a future recurrence risk if immunity remained unrestrained long-term and continually active T cells were not rested. They therefore sought to retain T cells in long-term memory. Once cancer is controlled or eliminated, immunity would tell them to stop, while enabling renewed readiness to attack if cancer returns. These are called immune memory cells (memory T cell).

Researchers thought a treatment was needed to help the many T cells activated by immunotherapy become memory cells after fighting cancer. For this purpose, they considered administering vitamin D , known to reduce inflammation in the body. It was thought capable of braking immunity. Researchers examined whether vitamin D could prevent recurrence in cancer patients receiving immunotherapy and how long afterward it should be given to preserve the memory pool most effectively long-term. The study also revealed that conversion of active cancer-killing T cells to memory cells involves regulatory T cells (Treg). Without them, active T cells break down, burn out and cannot become memory cells. Memory cells could therefore form only with regulatory T cells. Increasing their memory-accelerating function transformed active attacking T cells into memory cells. Battle-weary active T cells were thus kept dormant until another cancer cell attack. Researchers wanted to see whether vitamin D and regulatory T cells could combine to slow immunity at the right time. Because vitamin D is easy to administer, it is thought possible to brake immunity when desired.

Dear friends, more research is needed to better observe vitamin D's general role in our bodies and the continuity of immune memory, followed by its effects in immunotherapy. However, I believe that one day the immune system, effective in eliminating many diseases, will also defeat cancer irreversibly.

In a previous article, we shared “how vitamin D supplementation reduces inflammation in the body.” To access it, click here.