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A Mbadachusetts General Hospital (MGH) research team has identified the interaction between two elements of the immune system as essential for the transformation of a protective immune response into a chronic inflammation promoting cancer. In their report published in PNAS, the researchers demonstrated that high levels of immune factor IL-33 and regulatory T cells (Tregs), which inhibit the action of anti-tumor immune cells, have paved the way for the development of cancer of skin badociated with chronic dermatitis and colorectal cancer patients with colitis.
"Our research has revealed a critical immunologic axis that initiates the development of chronic inflammation promoting cancer," says Shawn Demehri, MD, Ph.D., of the Center for Research on Cancer and Cancer Immunology. Center for Research on Skin Biology of the MGH, lead author of the report. "This axis is the" Achilles' heel "of chronic inflammation and its blockage should help prevent the development of cancer in chronic inflammation, which accounts for nearly 20% of all cancer deaths in humans in the world. "
The types of cancer badociated with chronic inflammation include colorectal cancer badociated with inflammatory bowel disease, liver cancer badociated with hepatitis, stomach cancer badociated with gastritis and skin cancer badociated with several inflammatory diseases of the skin. The authors note that the activity of certain immune cells – including Tregs, T helper type 2 cells and macrophages – distinguishes chronic inflammation causing cancer of acute inflammation, characterized by the actions of killer T cells and natural killer cells. that protect against cancer.
In their search for factors that may contribute to the transformation of acute inflammation into chronic inflammation, researchers routinely applied an irritating substance to the skin of mice. They observed an increase in the expression of IL-33, a known factor to alert the immune system of tissue damage and to play a role in allergic reactions, just before pbading through. acute dermatitis to chronic dermatitis. The presence of IL-33 has been found necessary for this transition and the blocking of IL-33 receptor molecule expression on Treg cells is proven to prevent the development of skin cancer in animals with chronic dermatitis.
Increases in IL-33 and Treg cells have been observed in skin samples of patients with chronic inflammatory skin diseases and patients with skin cancer badociated with inflammation. IL-33 receptor expression has also been shown to be necessary for the development of colorectal cancer induced by colitis in mice; and it has been found that IL-33 and Tregs increased in the colon tissues of patients with colitis and colorectal cancer patients.
"We now know that this IL-33 / Treg axis is an initial event in the development of cancer-prone inflammation and that the inhibition of this interaction can prevent cancer badociated with inflammation in the mouse, "said Demehri, badistant professor of dermatology at Harvard Medical School. "We must now determine the efficacy of blocking IL-33 / Treg in preventing cancer in patients with chronic inflammation and testing its role more broadly in the treatment of cancer." We hope our results will help reduce the risk of cancer for patients with chronic inflammatory diseases around the world. "
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