RNA molecule helps skin cancer cells evade the immune system
Researchers at KU Leuven have identified an RNA molecule that enables melanoma — a type of skin cancer — to hide from the immune system. When this molecule, named LISRR, is blocked, immune cells are once again able to detect and attack the tumour. These findings offer promising directions for improving current immunotherapy treatments. The study was published in the Journal of Experimental Medicine.
The development of therapies against immune checkpoints has revolutionized the treatment of melanoma, an aggressive form of skin cancer. Despite this, the number of patients benefitting from this treatment is limited by treatment-related toxicities and the activation of diverse immune suppressive pathways. The KU Leuven team investigated how tumour cells contribute to anticancer immune suppression and discovered that the RNA molecule LISRR is only produced in tumour cells and not in healthy tissue. LISRR changes how certain proteins are made in the cell, boosting the production of molecules that suppress the immune system — allowing the cancer to grow unchecked.
RNA is a molecule found in every cell of the body. It plays a key role in translating genetic instructions into action. Some types of RNA, such as LISRR, do not produce proteins themselves but instead control how proteins are made in the cell. Increasingly, researchers are discovering that these non-coding RNAs can influence diseases like cancer — for example, by helping tumour cells resist treatment or evade immune responses.
Lifting the tumour’s shield
The researchers tested the effect of turning off LISRR in both human cancer cells and preclinical patient-derived models. In both cases, immune cells regained the ability to attack the tumour. The cancer cells also became more sensitive to existing immunotherapies.
"We found that LISRR do not affect the viability of tumour cells per se, but it actively protects them from immune attack," says Professor Eleonora Leucci (KU Leuven). "By blocking LISRR, we can remove that protective shield."
Potential beyond melanoma
The findings show that LISRR plays a key role in helping melanoma avoid immune responses. However, more research is needed before any clinical applications can be developed. The safety and effectiveness of potential treatments must still be thoroughly investigated. In future work, the researchers will also examine whether LISRR plays a similar role in other types of cancer where the molecule is also present.
More information
The study was published in Journal of Experimental Medicine under the title “The assembly of cancer-specific ribosomes by the lncRNA LISRR suppresses melanoma anti-tumour immunity” (DOI: 10.1084/jem.20251507).
The research was conducted at KU Leuven, in collaboration with the VIB-KU Leuven Center for Cancer Biology, the IEO European Institute of Oncology in Milan, and TransCure bioServices in France. The study was supported by funding from Belgian Federation for Cancer, and the Research Foundation – Flanders (FWO).