Amaia Lujambio and Marina Ruiz de Galarreta, researchers at Mount Sinai Hospital (New York, USA) and former students of the School of Sciences of the University of Navarra, have identified the first mechanism by which some liver tumors are resistant to immunotherapy. This finding, published in the journal Cancer Discovery, presents a sophisticated liver cancer mouse model that allows the study of how different alterations in tumor cells affect the response to immunotherapy.

The novelty of this model lies in the use of mice whose livers are genetically modified after birth, using CRISPR-Cas9 technology. "With this system, liver tumors can be generated that show the same alterations as hepatocellular carcinoma patients. As mouse tumors are simpler than patient tumors, we can draw conclusions that in human tumors would be more difficult, as there are many confounding factors," explains Dr. Marina Ruiz de Galarreta, first author of article.

The research led by the scientists from Navarra reveals for the first time that the activation of a gene (CTNNB1) produces tumors that do not respond to immunotherapy due to a defect in the recruitment of dendritic cells, which are necessary to develop an anti-tumor immune response. "Activation of beta-catenin generates a tumor microenvironment that excludes or repels immune cells. Therefore, even if we remove the "protective layer" of the tumor with immunotherapy, that doesn't work because immune cells can't reach the tumor. More importantly, the immune cells have not been trained to attack the tumor," stresses Dr. Marina Ruiz de Galarreta.

This finding represents an important advance in the fight against cancer and will allow the development of new personalized therapies aimed at attacking the most resistant tumors.

The researchers who took part in this study were Pedro Molina-Sánchez, Katherine Lindblad, Erin Bresnahan, Amaia Lujambio, Marina Ruiz de Galarreta and Lauren Tal Grinspan.