UCLA Researchers Find Pathway Driving T-Cell Exhaustion in Cancer Immunotherapy
UCLA researchers have identified a molecular pathway called CRL5 that contributes to T-cell exhaustion in cancer patients. Blocking this pathway may improve the effectiveness and durability of immunotherapy treatments for solid tumors.
Why it matters
This discovery could significantly enhance the success rates of CAR T-cell therapies, offering a more effective way to treat aggressive solid tumor cancers.
Researchers at the UCLA Health Jonsson Comprehensive Cancer Center used a CRISPR screen to identify a key molecular pathway that drives exhaustion in cancer-fighting immune cells, limiting their ability to keep tumors under control.
In the study , published in the journal Cancer Immunology Research, a journal of the American Association for Cancer Research, investigators found that blocking the pathway, known as the Cullin-5 RING E3 ligase complex (CRL5), allowed engineered immune cells to stay active longer, produce stronger anti-tumor responses and resist exhaustion in preclinical models.
The discovery could help researchers develop longer-lasting immunotherapies for solid tumors, including CAR T-cell therapies and other forms of adoptive cell therapy.
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