ITHACA, N.Y., July 5 — Inside a rare and aggressive liver cancer that primarily strikes children and young adults, scientists have mapped out a cellular trap. Fibrolamellar carcinoma accounts for roughly 2% of all liver cancer cases. There is no cure.
By the time it is found, the disease has often already spread. Now, a study published in the journal Gastroenterology offers one of the clearest explanations yet for why standard immunotherapy has struggled against this cancer.
Researchers from Cornell University and the University of Washington discovered that the tumor protects itself by blocking immune T cells from reaching it. Instead, the cancer redirects those cells into nearby fibrous tissue, trapping them there. The process is called T cell exclusion.
It may explain why immune checkpoint inhibitors — a common form of cancer immunotherapy — have shown limited success against fibrolamellar carcinoma. To understand how this happens, the team used single-nucleus transcriptomics, a technology that analyzes gene activity in individual cells.
The technique revealed that altered liver stellate cells produce the fibrous bands that give the cancer its name. Those same cells release signals that draw T cells away from the tumor. Then the researchers tested AMD3100, a drug already approved by the FDA.
Working with slices of tumor tissue taken from patients, they found that the drug blocked the signals trapping T cells. Once the signal was cut, the immune cells moved back into the tumors. When the team combined AMD3100 with immune checkpoint inhibitors, they observed stronger T cell activity and a significant increase in cancer cell death compared with immunotherapy alone.
The findings suggest that targeting T cell exclusion could improve treatment outcomes for this rare disease. Researchers caution that further studies are needed before the approach can become a standard therapy. Consult your doctor for medical advice.
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