Mayo Clinic finds TRAILshort protein acts as immune off switch that weakens CAR-T

Mayo Clinic researchers report that TRAILshort functions as an immune off switch that stops T cells from attacking cancerous and virus-infected cells and weakens CAR-T therapy, SciTechDaily reported, citing the Journal of Clinical Investigation. In preclinical models, blocking the protein restored T-cell activity. Elevated TRAILshort appeared in melanoma, lung, breast, pancreatic, and ovarian cancers and Hodgkin lymphoma, and also in COVID-19, tuberculosis, and hepatitis C. The team found TRAILshort activates SHP-1, a molecular brake that switches off T cells. Lead author Shahrzad Jalali said the work is the first to show TRAILshort acts as a signaling molecule that directly suppresses T-cell activity, not only blocking cell death. Senior author Andrew Badley said the protein shows up across cancer and misfiring-immune conditions. Co-author Saad Kenderian said targeting it could strengthen CAR-T. Further work is needed on safety and efficacy in patients.