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Melanoma dodges immune attack

Thu, 11th Oct 2012

Chris Smith

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Melanoma skin cancers dodge immune attack by adopting a chemical disguise, new research has revealed.

In recent years, doctors have made significant Melanomaprogress in cancer treatment by triggering the immune system to attack tumours. But these strategies, while often successful in the short term, are often blighted by relapse and the later return of the cancer.

Previously, this had been put down to the survival of a sub-population of malignant cells within a cancer that, by chance, were invulnerable to the therapy and could subsequently re-kindle the disease.

But now new research carried out by University of Bonn scientist Jennifer Landsberg and her colleagues suggest that something altogether more cunning is taking place. Using animals with the mouse equivalent of melanoma, the German team administered immune cells pre-programmed to attack the tumours.

Initially, the immune response was very successful, removing visible tumours from the animals. But just like in humans receiving these sorts of treatments, the animals usually later relapsed.

Careful examination of the tissues, however, showed that, in response to the immune attack, some of the cells in the tumour were switching off the very chemical markers that singled them out to be cancerous, rendering them invisible to the immune response.

This was enabling them to dodge the targeted immune therapy. When the onslaught was over, however, the cells re-upregulated their original markers and re-established the disease.

The cause, the team found, is a signalling chemical called TNF-alpha, which is used by the immune system to control its attack. By tuning into this signal and then chemically "ducking" by deactivating the very markers the immune system was looking for, the persistent tumour cells were able to escape.

Intriguingly, human melanoma cells also respond in the same way, the scientists show in their paper, published in Nature.

This suggests that immuno-therapy, as this field is known, needs to take these responses into account and, when engineering anti-cancer treatments, scientists need to programme the immune system against additional markers so that cells can't so easily disguise themselves in future...



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