Combining 5-fluorouracil and IL-1 beta inhibitor can improve effectiveness of chemotherapy

Published on December 5, 2012 at 1:18 AM · No Comments

These results reveal how the immune system can then limit the effectiveness of some cancer chemotherapies. The researchers now intend to block the molecules responsible for negative immune system activation to increase the efficiency of chemotherapy. A clinical trial to test this hypothesis should begin very soon.

Chemotherapy is one of the most frequently used treatments to eliminate cancerous cells. These drugs kill all cells that are multiplying, or block their proliferation (for example, cells responsible for hair growth, explaining the hair loss of treated patients). In addition to their direct toxic effects, the chemotherapeutic agents also seem to act on the immune system and could make it possible for the body to trigger a direct antitumor immune response in a second phase. However, this last point is still the subject of hot debate, since some studies suggest, conversely, that chemotherapy eliminates all immune defences.

What now?

The Inserm team directed by Professor Fran-ois Ghiringhelli (Inserm unit 866 "Lipids, nutrition and cancer") from the Georges Fran-ois Leclerc Cancer Research Centre in Dijon observed that two chemotherapeutic agents, 5-fluorouracile and gemcitabine, used to treat colon, breast and pancreas cancers activate a protein complex "inflammasome NLRP3" within some cells in the immune system.

To be more specific, this activation leads to releasing proinflammatory cytokine (interleukin IL-1beta) through these cells. This cytokine "distorts" the immune response related to lymphocytes T and causes the production of another cytokine (cytokine IL-17), which has protumoral properties by encouraging tumour angiogenesis, i.e. vascular irrigation of tumours.

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