Immunotherapy liver damage may be reduced by blocking receptor, study finds
UT Health San Antonio researchers report that LTβR blockade may limit liver toxicity while preserving anti-tumor T cells.
By Tom Brennan · Health & Medicine Correspondent
3 min read
Immunotherapy liver damage may be reduced by blocking a receptor that helps harmful immune cells persist, according to researchers at UT Health San Antonio. The finding matters because some cancer immunotherapies can help the immune system attack tumors while also triggering organ-damaging inflammation that can force patients to stop treatment or take broad immune-suppressing drugs.
The study, led by Sergey A. Shein and Alexei V. Tumanov of the Department of Microbiology, Immunology and Molecular Genetics at the Joe R. and Teresa Lozano Long School of Medicine, was published in Science Advances. UT Health San Antonio is the academic health center of The University of Texas at San Antonio.
According to the research team, the toxicity is tied to a group of T cells that are not aimed at tumors. These “bystander” T cells expand after immune activation, travel to the liver and promote inflammatory injury, the investigators reported.
How could immunotherapy liver damage be reduced?
The researchers found that the damaging T cells depend on the lymphotoxin beta receptor, or LTβR, in lymphoid organs including the spleen. Blocking that pathway reduced the problem T cells before they reached the liver, while preserving tumor-specific T cells that attack cancer, according to the study.
Immunotherapy works by using the body’s immune defenses to identify and destroy cancer cells. UT Health San Antonio said the same immune activation that helps fight tumors can also cause wider inflammation, including liver toxicity.
The study focused on immune responses linked to CD137, a receptor on T cells that can be targeted to boost cancer-fighting activity. The researchers reported that activating CD137 can also stimulate bystander T cells, creating a route to liver inflammation.
Shein said, according to UT Health San Antonio, that immunotherapies activate T cells that can attack tumors but may also set off immune activity in unwanted places. Tumanov said the work addresses a central problem in cancer immunotherapy: separating protective immune effects from damaging ones.
Why LTβR blockade differs from broad immune suppression
Current treatment for immune-related side effects often uses corticosteroids or other broad immunosuppressive drugs, according to UT Health San Antonio. The university said those treatments can weaken protective immune responses and raise infection risk.
The LTβR strategy described in the study is narrower. Rather than broadly suppressing immunity, the researchers said the approach aims to reduce persistence of nontumor-specific T cells while keeping the tumor-directed immune response intact.
Shein described the approach, according to UT Health San Antonio, as a way to filter immune activity rather than shut it down. The goal, the university said, is to adjust the survival threshold for harmful bystander T cells.
The findings do not establish a new clinical treatment yet. UT Health San Antonio said additional studies and clinical trials are needed before the approach could be used to make immunotherapies safer or guide new strategies for cancer and other immune-related diseases.
The paper is titled “Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.” Its DOI is 10.1126/sciadv.aea8737.
This story draws on original reporting from Medical Xpress.