Researchers have developed a greater understanding of the role interleukin (IL)-33 plays in driving the chronic inflammation that can promote skin and other cancers. This discovery has revealed potential targets for prevention or treatment, say investigators. In a press release from Massachusetts General Hospital in Boston, the investigators explain that IL-33—often released by epithelial cells when stressed or injured, triggering an inflammatory response—also acts within a cell’s nucleus. Inside the nucleus, the molecule may affect the expression of genes. The research team, in a paper published online in The EMBO Journal (Feb. 22, 2021), detail the findings from experiments in human epithelial cells of the skin and pancreas, as well as in mice, to determine whether IL-33’s actions in the nucleus of cells may contribute to cancer. They found that when they activated nuclear IL-33 under chronic inflammatory conditions, the SMAD signalling pathway was modified. Those alterations stimulated abnormal cell growth and division, ultimately resulting in cancer in the models. This observation suggests that inhibiting the expression or function of IL-33 within the nucleus of cancer-prone cells may help prevent cancers associated with inflammation, they write. “Our research has led to the discovery of a new mechanism by which immune factors can cause cancer development, and our findings point to a novel target for cancer prevention in chronic inflammation,” said senior author Dr. Shawn Demehri, in the release. Dr. Demehri is the director of the High Risk Skin Cancer Clinics and Center for Squamous Cell Carcinoma of the Skin at the Massachusetts General Hospital Cancer Center, and an associate professor of dermatology at Harvard Medical School, Boston. The team’s research was supported by National Research Foundation of Korea; the Howard Hughes Medical Institute; the Burroughs Wellcome Fund; the Arthur, Sandra and Sarah Irving Fund for Gastrointestinal Immuno-Oncology; the Sidney Kimmel Foundation; and the U.S. National Institutes of Health.