Vaccine hope for Tasmanian devil facial tumour disease

Researchers have shown that the Tasmanian devil facial tumour disease (DFTD) has developed a cunning strategy to evade the immune system, making it a highly infectious and deadly pathogen.

Cancers that pass between individuals as an infectious cell line are very unusual. DFTD is one such contagious cancer that emerged 16 years ago and is driving the Tasmanian devil to extinction.

When acting as a pathogen and as a transplant (allograft), DFTD cells should be rejected by the host’s immune response, yet DFTD causes all infected devils to die with no apparent rejection of tumour cells.

Why DFTD cells are not rejected has been a question of considerable confusion.

The immune system normally detects and destroys foreign cells by detecting the molecules of the major histocompatibility complex (MHC) on the surface of cells. In this way most cancers are prevented from spreading between individuals.

This research shows that DFTD cells don’t present these molecules on their surface, in vitro or in vivo, because of the down regulation of the expression of several genes. These genes, such as β2-microglobulin and transporters associated with antigen processing, are essential to the MHC antigen-processing pathway.

This finding explains how the cancer cells can be transplanted between devils without being rejected by the devil’s immune system.

“It is due to the nature of the cancer cells and not due to any defect in the devil’s immune system,” explained Professor Greg Woods, Principal Research Fellow at Menzies Research Institute Tasmania who was involved in the research. “By turning off immune recognition genes, such as MHC genes, the cancer cells are invisible to the devil’s immune system.”

The loss of gene expression is not due to structural mutations, but to regulatory changes such as deacetylation of histones. The researchers showed the MHC class I molecules could be restored to the surface of DFTD cells in vitro by using recombinant devil IFN-γ, which is associated with up-regulation of the MHC class II transactivator, a key transcription factor with deacetylase activity.

“… an encouraging aspect was that these genes can be turned back on and therefore they should become visible to the devil’s immune system. This provides an avenue towards the development of a vaccine,” said Woods.

This work was recently published in PNAS.