Cancer ‘master control switch’ could help tumours hide from immune system

US and German scientists have found a crucial link between a gene often found to be overactive in cancer cells, and tumours’ ability to hide from the immune system.

“The study suggests that drugs which help the immune system break through cancer’s defences may be more effective in patients whose cancers contain faulty Myc” – Professor Martin Glennie, Cancer Research UK

The discovery, in studies on mice, highlights the growing importance of treatments that activate patients’ immune system – so-called immunotherapies.

Experts hope the “exciting” findings may help pave the way for new treatments to be developed.

Published in the journal Science, the study centres on Myc, a cancer-associated gene. Faults in Myc can cause it to be overactive, triggering uncontrolled cell growth by switching on other genes that cause cells to divide.

The researchers, from the Stanford University School of Medicine and the University of Wurzburg, found that Myc switched on the production of two important molecules on the surface of cells, each of which control how the immune system reacts to a tumour.

The team described the first, called CD47, as a ‘don’t eat me signal’ that directs certain immune cells away from destroying the cell.

The second, PD-L1, is a ‘don’t find me signal’, able switch off immune cells.

Notably, PD-L1 is the target of immunotherapy drugs that aim to disable the switch and reveal cancer cells to the immune system. And the study suggests that targeting both Myc and the CD47 and PD-L1 molecules may slow or stop tumour growth, while spurring the immune system into action.

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Study leader Professor Dean Felsher, from Stanford University, said the findings describe an “intimate, causal connection” between how genes like Myc cause cancer, “and how those cancer cells manage to evade the immune system.”

Commenting on the discovery, Professor Graham Packham, a University of Southampton-based molecular oncologist, said: “Myc is faulty in the majority of cancers. And as a ‘master control switch’, it’s involved in many different jobs within a cell, including controlling how quickly the cell divides.”

His Southampton colleague, Cancer Research UK’s Professor Martin Glennie, an expert in cancer immunology, stressed that while the study was “important”, developing drugs to do this in patients has so far been unsuccessful.

“What we need now are good drugs to target Myc. It’s early days, but the study also suggests that drugs which help the immune system break through cancer’s defences may be more effective in patients whose cancers contain faulty Myc.

“This is really exciting, because we know that when the immune system is able to attack cancer then the patient is more likely to have a lasting response to treatment,” Glennie said.

According to Professor Packham, the finding reinforces the important role Myc plays in cancer. But further studies will need to focus on whether the same controls occur in people, he added.

“What this study in mice shows is that Myc may also help cancer cells avoid the immune system, adding to our understanding of how faulty Myc helps cancer cells grow,” he said.

“The next step will be to see if this is also true in patients, which could open the door to new treatments.”