21 February 2019
Cytokines and protective mechanisms of tumour cells
Published online 26 March 2014
Cytokines are chemical messengers released by or attached to the surface of cells. Although some may prove useful to tumour cells, most cytokines help the immune cells in their fight against them. To defend themselves against these immune cells, tumour cells can alter their chromosomes, affecting genes that secrete these cytokines and modifying the local microenvironment inside the tumour.
A team of researchers, led by Jérôme Galon from the French National Institute of Health and Medical Research (INSERM) in Paris, and including Arash Rafii from Weill Cornell Medical College in Qatar, examined the network of changes to cytokines, as well as the immune environment, inside colorectal tumours, publishing their findings in Science Translational Medicine.
The team found changes in the expression of 13 different cytokines, including IL-15, which was found to be of particular importance owing to its effect on the proliferation of immunity B and T cells. Patients with gene deletions in the chromosome site encoding IL-15 were found to have a higher risk of tumour recurrence and an overall lower survival rate. The opposite was true for patients with higher expression of IL-15.
"IL-15 expression and lymphocyte proliferation within the tumours seem essential for long-term survival of cancer patients," says Galon.
The findings suggest that tumour cells may use chromosomal instability as a means to evade protective anti-tumour immune mechanisms, and that therapies based on the enhancement of IL-15 levels may serve as an effective treatment for cancer.
- Mlecnik, B. et al. Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients. Sci. Transl. Med. 6, 228ra37 (2014).