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How supporting cells of the tumour kill the killers

last modified Mar 19, 2018 05:12 PM

Cancers have developed numerous ways in which to prevent our defences, that is our immune system, from destroying a Nature Communications logotumour. Many immune populations are found within a tumour, but it is the T cells that can ultimately decide tumour fate, and thus tumours frequently suppress their function.

A tumour is much more complex than a collection of cancer cells with many other cell types needed – these cells support the tumour in numerous ways and are known as the stroma. One population of supporting stromal cells, the cancer associated fibroblast, is associated with poor patient survival. T cells are often found near cancer associated fibroblasts, raising the possibility that cancer associated fibroblasts may help the tumour by interfering with our immune system.

New research by the Shields group has shown that cancer associated fibroblasts are able to eat tumour cell debris and present the material to T cells entering the tumour. This presentation process would normally instruct T cells to proliferate and activate so they can destroy their targets. However, in the tumour, cancer associated fibroblasts present material along with a negative signal through molecules FASL and PDL-2, which instead tells T cells to die, and allows the tumour cells to continue growing.

The mechanisms identified show for the first time that cancer associated fibroblasts directly interact with T cells to mediate immune suppression within the tumour but also helps to explain why in why cancer associated fibroblasts are associated with poor survival.

The study entitled Cancer-associated fibroblasts induce antigen-specific deletion of CD8+ T Cells to protect tumour cells by Lakin et al. has been published in Nature Communications on 5 March, 2018.