Researchers re-train immune cells to fight disease
20 May 2008
Researchers have found a way of changing the behaviour of immune cells during infection and cancer to help the fight against disease. They targeted cells known as macrophages that can either fight a tumour or infection or encourage it to spread. The findings in the Journal for Experimental Medicine could have important implications for future tumour therapy.
The macrophage immune cells can destroy tumour cells and invading bacteria by producing toxic inflammatory proteins. But some pathogens and the environment inside the tumour renders these cells impotent by somehow halting this production.
Now scientists at Queen Mary's University London (QMUL) have identified a key protein known as IKKβ which is involved in determining the macrophages' ability to attack tumour cells and fight infection. By inhibiting IKKβ, the researchers were able to 're-educate' macrophages so that they behave in the classical way, as a vital part of the body's immune response. The research was funded by the Medical Research Council and by the Wellcome Trust.
Dr Toby Lawrence, MRC New Investigator Award holder who helped lead the research, believes that as well as providing valuable insights into how to boost immunity in infection, the findings may have important implications for drug development for the treatment of chronic inflammatory diseases, such as rheumatoid arthritis. Because the role of IKKβ differs depending on the context, inhibiting its action may lead to an increase or decrease in inflammatory proteins depending on the role of macrophages in the disease.
"Many big pharmaceutical companies have advanced programmes to develop IKKβ inhibitors, focusing on chronic inflammatory diseases," says Dr Lawrence. "Our research indicates that in chronic inflammatory diseases, inhibiting IKKβ may lead to more inflammation, causing adverse effects. In other infections, however, an inflammatory response is how our body fights back."
In a parallel study, a second team at QMUL, led by Dr Thorsten Hagemann, has found that IKKβ can play a similar role in blocking the ability of macrophages to fight tumour cells.
Dr Lawrence said: “We have identified a protein from cancer cells that blocks the anti-tumour and anti-microbial activity of macrophages, it will be interesting to find out how pathogenic organisms and cancer cells have evolved to hijack this pathway and protect themselves from attack by our immune system, this will give us clues on how to boost immunity in infection as well as cancer.”
Original research papers: ‘‘Re-educating’’ tumour-associated macrophages by targeting NF-ĸΒ and An antiinflammatory role for IKKß through the inhibition of ‘‘classical’’ macrophage activation are published in the Journal of Experimental Medicine.
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