Shadowy cells may be betraying the body by protecting cancerous tumours from the wrath of the conventional immune system. If we could block these cells, treatments for stopping tumour growth could follow.
Cancerous tumours are always found surrounded by a mixture of immune cells that, for some unknown reason, seem to stand back and allow the tumour to grow without interfering.
鈥淲e knew the tumour鈥檚 microenvironment is immunosuppressive, but we didn鈥檛 know how,鈥� says at the University of Cambridge. To find out, his team investigated these surrounding cells.
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They decided to single out one type of cell that is present around tumours, as well as in areas of chronic inflammation, such as the joints of people with rheumatoid arthritis. Little is known about the cell, which the researchers call the FAP-expressing cell after the fibroblast activation protein found on its surface.
Although the cell was discovered lurking around tumours 20 years ago, there has been little research into its function, and it has mainly been used as a tumour marker, Fearon says. 鈥淲e鈥檙e still trying to work out if it鈥檚 been studied under a different name,鈥� he adds.
Taking them down
To work out the role of this cell, the group first injected mice with a lung or pancreas tumour below the skin and then selectively killed off FAP-expressing cells. To do this, they inserted a human receptor for diphtheria toxin 鈥� which doesn鈥檛 normally affect mice 鈥� in FAP-expressing cells only. When the researchers then infected the mice with the toxin, the FAP-expressing cells died 鈥� and all the lung and pancreas tumours stopped growing.
鈥淭he tumours normally double in size over two days,鈥� Fearon says. But when his group dissected the tumours two days after killing the FAP-expressing cells, the tumours were either the same size or slightly smaller than when they were first injected. 鈥淲e were surprised at how fast it worked,鈥� says Fearon.
What鈥檚 more, around half of the tumour cells in the treated mice were dead from oxygen starvation, suggesting their blood supply had been cut off.
The FAP-expressing cells might work by blocking the action of two proteins which normally work to kill cells. 鈥淲hen we blocked the activity of these two proteins[in a separate experiment], we prevented tumour necrosis,鈥� says Fearon.
at the Paterson Institute for Cancer Research at the University of Manchester, UK, points out that the mouse model of cancer 鈥渄oes not resemble the nature of human carcinomas that we often observe in the clinic鈥�.
Before the team can develop a therapy to try in humans, Fearon says they need to figure out where else the cells might reside in the body, and what they鈥檙e doing.
Journal reference: , DOI: 10.1126/science.1195300
