Mayo Clinic discovers TRAILshort immune off switch

Mayo Clinic researchers published a study in the Journal of Clinical Investigation identifying a previously unknown role for the protein TRAILshort, which acts as an immune 'off switch' by suppressing T-cell activity. The team, led by Andrew Bailey and Shahrzad Jalali, found that TRAILshort activates SHP-1, a molecular brake that prevents T cells from attacking cancer and virus-infected cells. Elevated TRAILshort levels were detected in melanoma, lung, breast, pancreatic, ovarian cancers, Hodgkin lymphoma, and infectious diseases including HIV, COVID-19, tuberculosis, and hepatitis C. In preclinical models, blocking TRAILshort restored T-cell activity and improved the effectiveness of CAR-T cell therapy. The findings suggest that targeting TRAILshort could enhance cancer immunotherapies and potentially be used to modulate immune responses in autoimmune diseases and transplantation. The research is part of Mayo Clinic's Precure initiative.