According to new research published in Cell, chemicals that attract specialized immune cells toward tumours could be used to develop better immunotherapies for cancer patients. The study findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumour-derived PGE2 for immune evasion and that could be exploited for cancer therapy.
Scientists at the Francis Crick Institute have discovered that immune cells called Natural Killer cells accumulate in tumours and release chemicals that attract specialized dendritic cells (cDC1) – white blood cells known for triggering anti-cancer immune responses – to a tumour.
Genes associated with Natural Killer cells and cDC1 correlated with cancer patient survival in a dataset of over 2,500 patients with skin, breast, neck and lung cancers. A similar correlation was seen in an independent group of breast cancer patients, with a particularly positive outcome for women with triple-negative breast cancer, which typically has a poor prognosis.
The findings have given us a renewed appreciation of the importance of Natural Killer cells and cDC1 in the immune response against cancer said Professor Caetano Reis e Sousa, Senior Group Leader at the Crick, who led the study. It is still early days, but attracting more cDC1 to tumours could be the basis of a new immunotherapy for cancer patients.
The team also showed that prostaglandin E2 (PGE2), a molecule produced by some cancer cells, suppresses Natural Killer cell activity and reduces the responsiveness of cDC1 to the chemical attractants. This suggests that blocking PGE2 with aspirin might help boost the effectiveness of immunotherapies by restoring cDC1 levels in tumours.
Researchers said they know a bit better how this key anti-cancer response works, and they can look at identifying other ways in which cancers get around it. This understanding will ultimately help to develop new immunotherapy approaches to help more patients.
The interesting research reveals more about the way the body's immune system interacts with cancer, exposing one way in which cancer can avoid the attack. Studies like this highlight the complexity of this relationship and may reveal another way in which the immune system can be harnessed to treat cancer. It is vital that work continues to help make immunotherapies more effective and beneficial to more patients.