Mayo Clinic finds protein that lets cancer evade immune system

Mayo Clinic researchers have identified a protein, TRAILshort, that cancer cells use to shut down the body's immune response, a discovery that could lead to more effective cancer immunotherapies. The finding was published in the Journal of Clinical Investigation. The study reveals TRAILshort acts as an immune "off switch" by activating SHP-1, a molecular brake that prevents T cells from attacking diseased cells. Blocking the protein restored T-cell activity in preclinical models, and elevated TRAILshort levels were found in melanoma, lung, breast, pancreatic and ovarian cancers, plus infectious diseases like COVID-19 and tuberculosis. Researchers found TRAILshort reduces the effectiveness of CAR-T cell therapy, suggesting targeted antibodies could improve treatment outcomes. The protein may also serve as a biomarker and offer a way to regulate immune activity in autoimmune diseases, though additional studies are needed to confirm safety and efficacy in patients.