A new study from Cornell University has identified a potential way to improve immunotherapy for fibrolamellar carcinoma, a rare and aggressive liver cancer that mainly affects children and young adults. The research, published on February 17 in the journal Gastroenterology, shows that an existing FDA-approved drug, AMD3100, could help immune cells better attack this type of tumor.
Fibrolamellar carcinoma represents up to 2% of all liver cancers and often spreads before it is detected. Currently, there are no effective treatments or cures for this disease, and patients typically face a poor prognosis.
The study explains that these tumors change their local environment in a way that prevents the body's immune T cells from reaching and attacking the cancer cells—a process called T-cell exclusion. Researchers found that AMD3100 can stop the tumors from isolating T cells, allowing them to move into the tumor's core where they can target cancer cells.
Immune checkpoint inhibitors are a form of immunotherapy designed to activate T cells against cancer. While these drugs have been successful in treating several cancers such as liver, lung, kidney, bladder cancers, and melanoma, some types—including pancreatic, prostate, and brain cancers—often resist this approach. The findings about how tumors sequester T cells may help explain why certain cancers do not respond well to immunotherapy.
The team tested AMD3100 on slices of patient tumors and observed that it enabled more T cells to reach the center of the tumor. When combined with immune checkpoint inhibitors, AMD3100 further increased T cell activation and led to higher rates of tumor cell death.
Researchers are now looking for clinicians who treat liver cancer patients interested in launching clinical trials for this new approach. "A compelling feature of this work is that AMD3100 is already FDA-approved, which can reduce risks and potentially speed up timelines for clinical trials in fibrolamellar carcinoma," said Sethupathy.
