sharon sanders
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Researchers discover immune ‘off switch’ used by cancer cells
Brittany Cordeiro
August 3, 2026
Mayo Clinic researchers have identified a protein that cancer cells use to shut down the body's immune response, a discovery that could help scientists develop new treatments that make cancer immunotherapies more effective.
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.
"What strikes me most is that TRAILshort appears in cancer, HIV, COVID-19, tuberculosis, lupus and Crohn's disease — almost every condition where the immune system is failing or misfiring. That tells us we may have identified a fundamental switch in human immunity, not just a curiosity in one disease," says Andrew Badley, M.D., senior author of the study. Dr. Badley is the HH Sheikh Khalifa Bin Zayed Al Nahyan Professor of Infectious Diseases and an immunologist at Mayo Clinic.
snip
https://newsnetwork.mayoclinic.org/...cover-immune-off-switch-used-by-cancer-cells/
https://www.jci.org/articles/view/194449
Researchers discover immune ‘off switch’ used by cancer cells
Brittany Cordeiro
August 3, 2026
Mayo Clinic researchers have identified a protein that cancer cells use to shut down the body's immune response, a discovery that could help scientists develop new treatments that make cancer immunotherapies more effective.
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.
"What strikes me most is that TRAILshort appears in cancer, HIV, COVID-19, tuberculosis, lupus and Crohn's disease — almost every condition where the immune system is failing or misfiring. That tells us we may have identified a fundamental switch in human immunity, not just a curiosity in one disease," says Andrew Badley, M.D., senior author of the study. Dr. Badley is the HH Sheikh Khalifa Bin Zayed Al Nahyan Professor of Infectious Diseases and an immunologist at Mayo Clinic.
snip
https://newsnetwork.mayoclinic.org/...cover-immune-off-switch-used-by-cancer-cells/
https://www.jci.org/articles/view/194449