Published in the Journal of Clinical Investigation, the study identifies a previously unknown role for a protein called TRAILshort, which acts like an immune “off switch.” The researchers found that TRAILshort prevents T cells—the immune system’s primary cancer-fighting cells—from recognizing and destroying cancer and virus-infected cells. In preclinical models, blocking the protein restored T-cell activity and improved immune response.

The researchers also found that TRAILshort reduces the effectiveness of chimeric antigen receptor-T cell therapy (CAR-T cell therapy), one of the most advanced forms of cancer immunotherapy. Their findings suggest that therapies designed to block TRAILshort could improve CAR-T treatment and potentially benefit other immune-based cancer therapies.