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Gluten contributes to the development of a very rare blood cancer

With funding from Worldwide Cancer Research, scientists in The Netherlands have revealed how gluten plays a role in the development of a rare form of cancer, for a small group of people with coeliac disease.

The scientists at Leiden University Medical Center (LUMC) have shown that immune system cells, which react to gluten, produce chemicals called cytokines that can contribute to the development of a rare form of lymphoma (cancer of the white blood cells). The findings were published recently in the Proceedings of the National Academy of Sciences (PNAS). LUMC researcher and Worldwide Cancer Research scientist, Dr Jeroen van Bergen, explained “the immune system is seen as an ally in the battle against cancer, but that isn’t always the case.”

Refractory coeliac disease

For some people, eating grains such as wheat, barley and rye, which contain gluten, can cause chronic inflammation in the small intestine. This condition is known as coeliac disease, an autoimmune disease, where special immune system cells, called gluten-specific T cells, have an extraordinarily strong inflammatory reaction to the gluten. The cells produce chemicals known as cytokines which can then stimulate other immune system cells.

Coeliac patients usually manage to control their symptoms by following a gluten-free diet. However, a small percentage (2-5%) of coeliac disease patients diagnosed in adulthood does not respond to such a diet and have what is called refractory coeliac disease (RCD). As these people are only diagnosed as an adult they will have been eating gluten over many years before, by which time the inflammation and long term damage may already have been done and therefore changing their diet at this point does not help. In one type of refractory coeliac disease, called RCDII, immature white blood cells from the immune system (called lymphocytes) which are located in the wall of the small intestine, multiply in number in an uncontrolled manner. In about half of these patients, these cells develop into a malignant, incurable form of white blood cell cancer called enteropathy-associated T-cell lymphoma (EATL), a very rare type of lymphoma arising from the inflammation caused by the body’s reaction to gluten.

EATL is an aggressive lymphoma and the future for these patients is not very good, meaning new treatments are urgently needed.

Growth factors

Scientists have known for a long time that in order to grow and survive, the lymphoma cells are dependent on a cytokine called IL-15 which acts as a growth factor, encouraging cells to multiply. Now the researchers have shown that the proliferation can be stimulated just as effectively by three other cytokines, TNF, IL-2 and IL-21. These three cytokines are produced by the gluten-specific T cells, which react to gluten. The new findings thus provide a potential mechanism by which the immune response to gluten contributes to the growth of malignant cells in RCDII.

Targeted treatments

An important question now is to find out at which stage of lymphoma development these cytokines are involved. Dr van Bergen explained: “It is likely that at the time of lymphoma diagnosis, the patient has already experienced decades of intestinal inflammation. We need to determine the extent to which it would actually help to block these newly discovered growth factors with targeted drugs at the time of diagnosis? In the meantime, we have tested a large number of potential drugs in the laboratory, and two of them seem promising. But as I said, this is only interesting in terms of a new treatment if these growth factors still have a role to play in the growth and development of the lymphoma after diagnosis.”

Dr Lara Bennett, Science Communications Manager at Worldwide Cancer Research added “this is another great example of the importance of early-stage, discovery research, like that funded by Worldwide Cancer Research. This is a rare type of cancer but the findings could be of real benefit to this small but important group of patients with refractory coeliac disease in the future.”

These findings from the researchers in Leiden and Amsterdam were published in the leading journal PNAS.

The research was funded by a grant from Worldwide Cancer Research.