Finding the flaw in cancer’s camouflage
“We had absolutely no idea that we were going to find this,” says Dr Payam Gammage, a group leader at the Cancer Research UK Scotland Institute. “It’s about as true a discovery as you could ever have.”
It came in three stages.
At first, everything was going as planned. The team, which also included scientists from Memorial Sloan Kettering Cancer Centre in the US, engineered their own mitochondrial mutations into cells in the lab and saw how they changed the way cells use energy.
“It’s still an important finding,” says Gammage, “but it’s what we expected.”
Then they looked closely at how these changes played out in mouse models. Gammage needs a stronger word than “important” to describe what that showed.
“We realised that there was this really profound effect happening,” he explains. “Tumours with these mitochondrial mutations activated the immune system, and tumours without these mutations didn’t.”
Here’s a way to picture that. Powerstations are big, noisy and connected to almost everything. Even masters of disguise like cancer cells can find them hard to camouflage.
So, when the mice’s immune systems were already suspicious of mitochondrial mutations, immunotherapy gave them the last bit of guidance they needed to start clearing out tumours. Tumours without these mutations were much less likely to respond to treatment.
Once that was clear, the question shifted to what this might mean for people. Gammage’s team went back to the earlier nivolumab study and re-examined the data according to what they had found.
In total, the treatment was 2.6 times more effective for people with high levels of mitochondrial DNA mutations.