Improving chemotherapy effectiveness by acting on the immune system

An Inserm team in Dijon directed by François Ghiringhelli is to publish an article this week in the Nature Medicine review. The article suggests that two chemotherapy drugs frequently used to treat digestive and breast cancers may encourage the development of tumors by modulating the anti-tumoral immune response.

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 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 . 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 .

What now?

The Inserm team directed by Professor François Ghiringhelli (Inserm unit 866 "Lipids, nutrition and cancer") from the Georges François Leclerc Cancer Research Centre in Dijon observed that two chemotherapeutic agents, 5-fluorouracile and , 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.

"Our results have made it possible to ascertain that the activation of inflammasome limits the effectiveness of chemotherapy. The challenge was then to see whether we could prevent the activation of inflammasome" explains François Ghiringhelli. The researchers then tested two different strategies:

The first was to test the two drugs on inflammasome NLRP3- or cytokine IL-17-deficient mice. In these cases, the researchers showed that antitumor activity was not only present, but it actually increased, demonstrating that these two elements (NLRP3 and IL-17) slow down the chemotherapy action.

The second strategy was to treat the mice using an IL-1beta inhibitor. Here again, the effectiveness of chemotherapy was again increased.

These results suggest that targeting the inflammasome and IL-1beta channels, combined with the use of these two chemotherapy agents, can improve the effectiveness of the latter. These tumour cells are eliminated and, in parallel, the damaging immune responses are deleted.

A therapeutic trial combining 5-fluorouracil and IL-1 beta is currently being prepared and should begin soon at the Georges François Leclerc Cancer Research in Dijon.

add to favorites email to friend print save as pdf

Related Stories

Novel cytokine protects mice from colitis

Aug 23, 2011

Inflammatory bowel disease (IBD), which affects more than 1 million patients in North America, results from an uncontrolled immune response triggered by environmental factors, such as bacteria, in people genetically predisposed ...

In response to chemo, healthy cells shield cancer cells

Oct 28, 2010

Many times, cancer patients respond very well to chemotherapy initially only to have their disease return, sometimes years later. Now researchers reporting in the October 29th issue of the journal Cell, a Cell ...

Recommended for you

Could trophoblasts be the immune cells of pregnancy?

Dec 18, 2014

Trophoblasts, cells that form an outer layer around a fertilized egg and develop into the major part of the placenta, have now been shown to respond to inflammatory danger signals, researchers from Norwegian University of ...

Moms of food-allergic kids need dietician's support

Dec 18, 2014

Discovering your child has a severe food allergy can be a terrible shock. Even more stressful can be determining what foods your child can and cannot eat, and constructing a new diet which might eliminate entire categories ...

Multiple allergic reactions traced to single protein

Dec 17, 2014

Johns Hopkins and University of Alberta researchers have identified a single protein as the root of painful and dangerous allergic reactions to a range of medications and other substances. If a new drug can ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.