Therapy resistance decoded
03.12.2012 - French researchers have identified how the body’s immune systems triggers therapy resistance to the cancer drugs gemcitabine and 5-fluorouracil.
The researchers, headed by François Ghiringhelli from INSERM in Dijon, found that in mice, the drugs activate a protein complex, termed Nlrp3 inflammasome, in myeloid derived suppressor cells. This activation leads to the release of the immune cell interleukin (IL)-1 beta, which then skews T immune cells to produce protumorigenic IL-17 and results in enhanced growth of tumours in mice (Nature Medicine, doi: 10.1038/nm.2999).
The chemotherapeutics were more efficacious at inhibiting tumour growth in mice lacking Nlrp3 or IL-17, or treated with an IL-1 receptor antagonist. The findings suggest that targeting the inflammasome pathway in conjunction with chemotherapy may improve its tumour killing efficacy by preventing the induction of protumorigenic immune responses.