How Tumors Fight Back

The immune system works remarkably well for most threats, but not against cancer. Many kinds of tumors can evade detection, and others fight back. Now Swiss researchers may have uncovered a particularly devious counterattack used by certain tumor cells: They can force cells of the immune system to commit suicide. The finding may explain why one of the most common forms of brain cancer is also the deadliest.

Aggressive tumors occur in 40% of brain cancer cases. The new findings, reported in the current issue of the Journal of Clinical Investigation, suggest that the main attackers, called astrocytoma cells, flourish by exploiting the immune system's own housekeeping process. During an infection, immune cells called T lymphocytes proliferate to fight a specific invader, but once the battle is won, the excess T lymphocytes must be eliminated to prevent damage to other cells. When a T lymphocyte encounters a protein called Fas ligand (FasL)--carried by other T cells--it self-destructs.

Phillipe Saas, Paul Walker, and colleagues at the University Hospital of Geneva found that astrocytoma cells also carry FasL on their cell surfaces, and they reasoned that this would produce the same self-destruct signal. To test that notion, the team used a genetically modified cell line that expressed the receptor for FasL found on T lymphocytes and mixed in FasL-bearing astrocytoma cells from mice, rats, and humans. The astrocytoma cells killed the target cells. And tumor cells taken from patients proved just as deadly.

To clinch the finding, the team must now show that FasL from tumors kills T lymphocytes in humans. "The real importance in the more complex situation of human cancer growth has to be intensively investigated," says Walker.

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