It is known that inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). But the underlying mechanism—and the genetic drivers—between this link remain yet to be determined. Genetic variants in TNFSF15, encoding tumor necrosis factor (TNF)-like cytokine 1A (TL1A), are associated with both severe IBD and advanced CRC. Now, a new study points to immune reactions in the gut—driven by a key signaling protein and a surge of white blood cells from the bone marrow—to help explain why people with inflammatory bowel disease have a higher risk of colorectal cancer. This work is published in Immunity in the paper, “Innate lymphoid cells activated by the cytokine TL1A link colitis to emergency granulopoiesis and the recruitment of tumor-promoting neutrophils.” IBD, which includes Crohn’s disease and ulcerative colitis, is characterized by chronic gut inflammation. Between 2.4 and 3.1 million Americans have the condition, according to the U.S. Centers for Disease Control and Prevention. IBD raises the risk of other autoimmune and inflammatory conditions and greatly increases the risk of colorectal cancer, which tends to occur at younger ages and with worse outcomes in patients with the condition. The research sought to explore how TL1A signaling promotes colitis-associated tumorigenesis. Experimental drugs that block TL1A activity have shown great promise against IBD in clinical trials, but how the signaling protein promotes the disease and associated tumors has been unclear. The work suggests that TL1A has much of its impact through the tissue-resident type 3 innate lymphoid cells (ILC3s) in the gut. Not…
