PGE(2) inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function. (https://pubmed.ncbi.nlm.nih.gov/38658764/)

These scientists wanted to understand why some treatments for cancer don't work as well as they could. They studied a type of immune cell called CD8(+) T cells, which are important for fighting cancer. They found that a molecule called prostaglandin E2 (PGE2) in the tumor environment can stop these immune cells from working properly.

The scientists discovered that PGE2 stops the immune cells from sensing another important molecule called interleukin-2 (IL-2), which helps the immune cells grow and fight cancer. PGE2 does this by blocking a part of the immune cells that is needed to sense IL-2. This causes the immune cells to die instead of fighting the cancer.

But the scientists also found a way to help the immune cells work better. By blocking the effects of PGE2, they were able to make the immune cells sense IL-2 again. This made the immune cells grow stronger and better able to fight cancer.

This study is important because it helps scientists develop new treatments that can make the immune cells more effective in fighting cancer. It gives hope for better ways to treat cancer in the future.

Morotti M., Grimm AJ., Hope HC., Arnaud M., Desbuisson M., Rayroux N., Barras D., Masid M., Murgues B., Chap BS., Ongaro M., Rota IA., Ronet C., Minasyan A., Chiffelle J., Lacher SB., Bobisse S., Murgues C., Ghisoni E., Ouchen K., Bou Mjahed R., Benedetti F., Abdellaoui N., Turrini R., Gannon PO., Zaman K., Mathevet P., Lelievre L., Crespo I., Conrad M., Verdeil G., Kandalaft LE., Dagher J., Corria-Osorio J., Doucey MA., Ho PC., Harari A., Vannini N., Bottcher JP., Dangaj Laniti D., Coukos G. PGE(2) inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function. Nature. 2024 May;629(8011):426-434. doi: 10.1038/s41586-024-07352-w. Epub 2024 Apr 24.