New Research Predicts Interaction Between Immune Factors May Induce A Chronic Inflammatory Response

Recently, scientists from the Massachusetts General Hospital have identified through research that the interaction between the two components of the immune system is important for converting a protective immune response into a chronic cancer-promoting response. Related research was published in the international journal Proceedings of the National Academy of Sciences. The researchers said that elevated levels of the immune factor IL-33 and regulatory T cells (Tregs) may inhibit the activity of tumor immune cells, which may contribute to the development of colorectal cancer in patients with chronic dermatitis-related skin cancer and enteritis.

According to Dr. Shawn Demehri, MD, ‘Our research reveals a key immune axis that can initiate the development of a chronic inflammatory disease that is a fatal cause of chronic inflammation, and blocking its function is expected to inhibit the development of cancer in chronic inflammation. At present, global chronic inflammatory cancer accounts for 20% of all cancer deaths. Types of cancer associated with chronic inflammation include colorectal cancer associated with inflammatory bowel disease, hepatitis-related liver cancer, gastritis-related gastric cancer, and skin inflammation-related skin cancer.

The activity of specific immune cells, including Tregs, type 2 T cells, and macrophages, which is effective in distinguishing between cancer-induced chronic inflammation and acute inflammation. The main feature of acute inflammation is that killer T cells and natural killer cells can express their activity to help the body fight cancer. In the search for factors that promote the transition from acute inflammation to chronic inflammation, the researchers regularly instill a specific substance into the skin of mice. They observed that an increase in the expression level of the immune factor IL-33 would call acute dermatitis conversion. Chronic dermatitis, which blocks the expression of IL-33 receptor molecules on the surface of Treg cells, can inhibit skin cancer in animals with chronic dermatitis.

IL-33 overexpression and Treg accumulation are associated with cancer-prone chronic ACD (allergic contact dermatitis) in human skin.

In addition, the researchers also observed an increase in the levels of IL-33 and Treg cells in the body of patients with chronic inflammatory skin diseases and inflammatory-associated skin cancer. Expression of the IL-33 receptor is required for colorectal cancer induced by intestinal enteritis in mice, and the researchers have also observed an increase in the levels of IL-33 and Tregs in the body of patients with enteritis and colorectal cancer. Researcher Demehri pointed out that now they know that the IL-33/Treg axis can turn on cancer-induced inflammatory events, and inhibiting the axis can inhibit the development of inflammatory-related cancers.

Researchers now need to determine the effectiveness of blocking IL-33/Treg axis inhibition of cancer in patients with chronic inflammation, and the role of this blockade as a cancer therapy. The researchers expect that the results of this study will help reduce the risk of cancer in patients with chronic inflammatory diseases worldwide.

Reference

Amir H. et al., IL-33/regulatory T cell axis triggers the development of a tumor-promoting immune environment in chronic inflammation, Proceedings of the National Academy of Sciences (2019).