Healthcare (Commonwealth Union) – Scientists from the University College London (UCL) have uncovered a novel technique to make cancer cells easier to detect by the immune system. This shows potential in making immunotherapy more effective for a wider range of tumors which can enhance patient outcomes.
The research explored a cellular process known as Nonsense-Mediated mRNA Decay (NMD) and it appeared in the publication Immunity. The process functions like an internal quality control system, seeking out and breaking down faulty RNA messages that have the ability to make proteins that are bad for cells or responsible for disease.
The scientists stated that NMD is essential for maintaining the cells’ ability to function normally, however it may also assist cancer cells avoid being detected by the immune system.
Immunotherapy treatments enhance the capability of the immune system to seek out and destroy cancer cells. They depend on tiny molecular markers, or antigens, that are on the surface of tumors indicating that something is wrong. However, a lot of cancers do not have a sufficient amount of these markers, making it difficult for the immune system to detect, which makes it possible for them keep growing.
Dr. Roberto Vendramin from the UCL Cancer Institute was the lead a group of scientists who found that halting the NMD process keeps defective RNA in tumors from being eliminated. This bad RNA is made use of to form proteins that do not work right. After that, these proteins are broken down into smaller pieces and put on the surface of cancer cells as antigens. This makes them easier for the immune system to see and makes immunotherapy work better.
Cancer cells do make faulty RNA under normal circumstances, but it breaks down quickly, stopping the production of abnormal proteins.
As a result, only a minimal number of antigens appear on the cell surface—too few for the immune system to detect. When NMD is inhibited, however, the faulty RNA persists, leading to the production of abnormal proteins that are processed and displayed as antigens on the cell surface.
Dr Vendramin pointed out that that while immunotherapy has significantly improved cancer treatment, many patients still see limited benefit because their tumours remain largely undetectable by the immune system and by stopping the breakdown of faulty RNA, these tumours can generate abnormal proteins that become antigens, making cancer cells easier for the immune system to identify. He further pointed out that boosting the number of visible antigens could help the body better target cancers, particularly those with low levels of genetic mutations.
“Once successfully developed into a treatment, our approach could benefit a wide range of cancer patients, particularly those whose tumours do not currently respond well to immunotherapy. It has the potential to improve immunotherapy response rates, which could translate into improved long-term survival and better outcomes for patients.”
Because this approach focuses on a shared characteristic of cancer cells—their tendency to generate defective RNA—it could be effective across a wide range of tumour types, rather than being confined to particular cancers. This broad applicability may be especially beneficial for patients whose tumours have relatively few DNA mutations, which account for most cancers and typically respond poorly to current immunotherapy treatments.
Researchers suggest it may be particularly useful for patients whose tumours already contain immune cells but are not being successfully controlled by them, such as certain colorectal, breast, and kidney cancers. It could also be combined with existing immunotherapies to boost their impact, even in cancers where those treatments already provide some benefit.
While the research is still in its early stages, interest is increasing in developing drugs that target the NMD pathway. Scientists believe promising candidates could emerge within the next few years, with early-stage clinical trials potentially beginning within around five years.
