Why the immune system ignores cancers

In a breakthrough that could hold the key to new ways to fight cancer, scientists have discovered that cancerous cells come with their own built-in immunosuppressants.  This explains why the body appears to allow cancers to run amok unchecked.

According to Cambridge University researcher Doug Fearon and his colleagues and writing in the journal Science, as cancers become established they recruit a population of cells known as mesenchymal stem cells from elsewhere in the body.  These stem cells pump out a chemical signal called alpha-FAP (fibroblast activation protein) which, the team have found, stops the immune system from reacting to the cancer.

The researchers made the discovery by creating two groups of genetically modified mice.  One group of animals were programmed to carry a gene encoding a glowing green protein that turned on whenever the alpha-FAP gene was active.  When foreign lung cancer cells were injected into these mice, the ensuing tumours also contained glowing green cells, indicating that the tumours had recruited cells from the host animal's body and those cells were making alpha-FAP.

In the second group of animals, rather than a glowing green gene, the researchers instead inserted a gene encoding a receptor for a toxin produced by diphtheria bacteria.  This had the effect of lethally sensitising any cells turning on their alpha-FAP genes to diphtheria toxin, which could be administered by injection, enabling the researchers to delete alpha-FAP positive cells at will.

Tumours implanted into these animals immediately stopped growing when the toxin was administered and the number of viable cells dropped by 60%.  Subsequent tests showed that the alpha-FAP-producing stem cells in the tumours were blocking the action of two key immune signalling molecules called gamma interferon and TNF-alpha.  When the rogue alpha-FAP-producing stem cells were destroyed by the toxin, however, the restoration of these signals led to rapid necrosis and subsequent immune control of the tumours. Since the same pathways exist in humans, targeting alpha-FAP could provide a promising new avenue with which to combat cancer.