Melanoma is a type of skin cancer that can be very dangerous because it often spreads to other parts of the body, as previously published in this newspaper. Normally, when cancer cells have many mutations, the immune system can detect them and kill them. In particular, special white blood cells called cytotoxic T cells are designed to recognize and destroy dangerous cells in the body. However, in many patients with melanoma, these T cells enter the tumor but still fail to kill it. Scientists have been trying to understand why this happens.
A recent study published in Cell by TelAviv University found that melanoma cells use a clever trick to avoid being killed by T cells. The researchers discovered that the tumor cells release certain molecules known as HLA (human leukocyte antigen) proteins in a way that misleads the T cells. Normally, HLA proteins help the immune system identify which cells belong in the body and which are dangerous. But in this case, melanoma cells send out decoy HLA signals that confuse T cells and stop them from doing their job effectively.
Inside a healthy immune response, cytotoxic T cells scan other cells for signs of infection or abnormality. They look at HLA proteins on the cell surface, which display tiny pieces of proteins from inside the cell. If the T cell thinks something looks wrong — such as pieces from a virus or an abnormal mutation — it will kill the cell. But melanoma cells in this study exported HLA proteins in a way that made the T cells “think” everything is normal, even though the tumor cells were not.
This decoy strategy means that the immune system can be present inside the tumor but unable to attack it properly. The cancer continues to grow and spread because the T cells have been tricked into ignoring it.
Understanding this deception is important for cancer research and treatment. Many modern therapies — such as immunotherapy — try to boost the immune system’s ability to fight cancer. But if tumors can send “fake” signals to confuse immune cells, this might explain why some patients don’t respond well to these treatments. By learning more about how melanoma cells export their HLA proteins, scientists hope to develop new drugs that can block this trick and help T cells recognize the real threat.
This study adds to our knowledge of the complex battle between cancer and the immune system. Future research will likely focus on ways to prevent melanoma cells from sending out misleading HLA signals or to make T cells better at spotting cancer even when decoys are present. Such advances could improve outcomes for people with melanoma and other cancers that use similar tricks.
Reference
- Chemla, Y., Itzhaki, O., Melamed, S., Weller, C., Sade, Y., Manich, P., Reshef, K., Xenidis, N., Maliah, A., Levy, G., Parikh, R., Bartok, O., Levy, O., Tal, I., Aziel, G., … et al. (2025). HLA export by melanoma cells decoys cytotoxic T cells to promote immune evasion. Cell. https://doi.org/10.1016/j.cell.2025.11.020
- Video: Prof. Carmit Levy explains a groundbreaking discovery revealing how melanoma cancer cells disable immune cells, a finding with major implications for future cancer treatments.
Editor of Daily 27.
Predoctoral researcher at the Department of Sociology in University of Barcelona.