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

_Sunday, August 9, 2026 at 12:02 PM EDT · Science · Latest · Tier 2 — Notable_

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.

## Sources

- [SciTechDaily](https://scitechdaily.com/cancer-cells-exploit-a-hidden-immune-off-switch/)

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Retrieved: 2026-08-09T22:57:19.138Z
Publisher: Tech & Business (techandbusiness.org)