Scientists have uncovered how the face-eating cancer threatening to wipe out the iconic Tasmanian devil (Sarcophilus harrisii) evades detection by the immune system.
The groundbreaking research, led by Marian Burr from the Peter MacCallum Cancer Centre in Melbourne, has also found some human cancers use the same hiding trick. But the team has discovered how to flush them out.
It all revolves around a marker the body uses to tag undesirable cells as fodder for the immune system.
When a cell gets infected with, say, a virus, proteins on its surface called the major histocompatibility complex (MHC) sound the alarm. That cues an influx of angry immune cells to subdue the foreign invader.
MHC on the surface of cancer cells also flags them as the enemy. But some cancers, including “small cell” cancer of the lung, are adept at hiding MHC from the immune system.
This nifty vanishing act helps the cancer grow and wreak havoc. It also explains why these cancers can shrug off the salvos of immunotherapy, a treatment that harnesses the body’s own immune system to destroy cancer cells. With the hostile MHC signal hidden, immune cells simply can’t locate the target.
That defence, however, may not be available for much longer – the researchers have found out how the cancer cells do it.
Those bad actors hack into a system of “Polycomb group proteins” that work as an on/off switch for genes. The cancer directs them to turn off the expression of MHC on their surface, rather like an enemy soldier casting off his uniform and changing into civvies.
Just like the military man in mufti, suddenly those cells are no longer targets.
All of which is bad news for patients. The researchers found one patient with small cell lung cancer had undergone precisely this silencing of MHC. The very same patient also failed to respond to immunotherapy.
“By avoiding recognition by immune cells, some cancers can continue to grow unchecked and are less likely to respond to new types of immune-based cancer therapies,” says Burr.
It is, quite literally, a diabolical device. The team found the ability to dodge immune bullets is shared by the Tasmanian Devil Facial Tumour, a cancer that has wiped out 75% of the famously feisty marsupial in little more than two decades.
“Similar to some human cancers, a defining feature of Tasmanian devil facial tumours is a remarkable ability to evade recognition and destruction by the immune system,” says Barr.
But the researchers have found a promising way of forcing cancer cells out of hiding.
Across several different cancer cell types, they used drugs to neutralise the polycomb proteins, pushing MHC back into the light where it could be seen by immune cells.
Senior author Mark Dawson thinks this tweak could be a game changer in some cancers.
“It is hoped this discovery may lead to a rationale for combining drugs that shut down the [Polycomb] pathway with immunotherapies to treat some aggressive cancers,” he says.
“This is especially important for solid cancers that are notoriously resistant to immune-based therapies, such as small cell lung cancer and some types of paediatric cancers, that have low expression of [MHC].”
The study appears in the journal Cancer Cell.
