New strategy to enhance the response to immunotherapy in liver tumors

Immunotherapy has changed the treatment of many cancers, but a significant number of patients do not respond because their tumors evade the immune system. Researchers at Cima Universidad de Navarra have developed a new strategy that enhances the response to immunotherapy in liver tumors. 

SLU7 is a protein whose expression is essential for the viability of solid tumor cells such as hepatocellular carcinoma, cholangiocarcinoma, colon cancer, among others. Its inhibition causes DNA damage, genomic instability, and alterations in the recognition of erroneous RNAs, which favors the appearance of neoantigens and the activation of innate immune response pathways, converting “cold” tumors into more inflamed tumors that are sensitive to immunotherapy.

“In this study, we have confirmed that by reducing SLU7 protein levels in tumor cells, we not only slow their growth, but also make them more visible to the immune system, allowing them to be recognized by the body's defenses,” explains Carla Rojo, predoctoral researcher in the Hepatology: Carcinogenesis and Liquid Biopsy Group at Cima and first author of the study. The results have been published in the scientific journal Biomedicine & Pharmacotherapy.

RNA-based therapies

Researchers have used different RNA-based approaches, including a chimeric molecule consisting of an aptamer targeting tumor cells linked to an RNA molecule (siRNA) against SLU7. “Our results show that SLU7 is an attractive target both as monotherapy and in combination with current treatments based on immune checkpoint inhibitors, and improves their efficacy,” says Dr. Carmen Berasain, principal investigator in the Cima Solid Tumors Program and director of the study.

The work was carried out within the framework of the Cancer Center Clínica Universidad de Navarra (CCUN) and the CIBER area of Liver and Digestive Diseases (CIBEREHD) and in collaboration with national and international centers, including the Icahn School of Medicine at Mount Sinai (New York) and the Complutense University of Madrid. The research received public funding from the Ministry of Science and Innovation and support from the Spanish Association Against Cancer (AECC).

Reference:

Rojo C, Otero A, Elizalde M, et al. Demonstration of SLU7 as a new cancer target. Biomedicine & Pharmacotherapy. 2025;193:118854. DOI: 10.1016/j.biopha.2025.118854