COULD the immune system be reprogrammed to fight cancer? It seems that macrophages – immune cells roped in by tumours to help them grow – can be turned into cancer killers.
Macrophages normally clean up dead and dying cells after an infection. In theory, macrophages should gobble up cancer cells too. “They should [swallow] dead and dying cancer cells, and stimulate an immune response against the tumour,” says David Ian Stott of the University of Glasgow, UK.
Instead, cancer cells release chemical signals that persuade macrophages to turn traitor, releasing growth factors that feed the tumour rather than destroy it. “Macrophages are educated by cancer cells to promote tumour growth,” says Thorsten Hagemann at Barts and The London Queen Mary’s Medical School in London. “If you remove macrophages from mice that are susceptible to cancer, they develop fewer tumours.”
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The trouble is that removing all macrophages would leave the body vulnerable to infection. “It would be better to alter macrophage behaviour to make them attack tumours,” says Hagemann, whose team has been trying to do just that.
They already knew that inhibiting a protein called NF-kB could slow tumour growth, but it now seems that one way it does this is by preventing macrophages from turning into tumour feeders.
Hagemann’s team engineered mice to produce macrophages that were missing a gene necessary to activate NF-kB. When they extracted the modified macrophages and injected them into mice with ovarian cancer, these modified macrophages triggered a strong immune response and tumour growth slowed significantly. The results were presented at the in Birmingham, UK, this week.
“The interesting thing is that the modified macrophages behave normally in healthy tissue, but if they are stimulated by tumour cells, they behave differently,” says Hagemann. “Instead of expressing molecules that encourage tumour growth they aggressively attack the tumour.” Macrophages are one of a growing number of immune cells that researchers are now trying to deploy against cancer. Last month the US Food and Drug Administration approved trials which will involve injecting immune cells called granulocytes from cancer-resistant individuals into people with cancer.
Martin Jadus of the Veterans Affairs Medical Center in Long Beach, California is enthusiastic about the macrophage approach. “If it’s true that macrophages can be re-educated to fight tumours, this could be an important advance,” he says.
