Pancreatic cancer is one of the most aggressive cancers and five-year survival rates are just 10%. A very small number of patients live longer, with less than 2% surviving more than 10 years after diagnosis. Researchers have been working to understand how this cancer is kept at bay for so long in these rare long-term survivors.
The key appears to be how the immune system recognises particular proteins on the tumours, called neoantigens. The immune system uses these neoantigens to identify and then kill the cancer cells. A new international study led by Memorial Sloan Kettering Cancer Center in New York, in collaboration with researchers at the Garvan Institute of Medical Research has shed light on this complex interaction between the immune system and pancreatic cancer.
“This is further evidence of just how important the immune system is in fighting cancer, and provides useful clues to how it can be harvested to work towards a cure”, says Professor Anthony Gill, Chairman of the Australian Pancreatic Cancer Genome Initiative and lab leader at Garvan.
The new study is published in the journal, Nature.
How the immune system fights pancreatic cancer
The researchers studied 15 patients with pancreatic cancer whose tumours returned a long time after surgery – in some cases more than 10 years later. By comparing the first tumour to the recurrence in these long-term survivors, the researchers showed that constant surveillance of the cancers by the immune system had changed the cancers themselves, via a process called immunoediting.
The immune system had picked up and destroyed the cancer cells with an abundance of neoantigens, causing the cancers to evolve to eventually show less of these neoantigens as they try to evade the immune system. Cancer immunoediting has previously been shown in mice, but this study provides the first indication that it occurs in humans.
“The immune system uses these neoantigens to kill the tumour cells that are most unlike normal cells, leaving behind the cancer cells that are harder to recognise” says Professor Gill. “It’s these ‘stealth cells’ that become invisible to the immune system that are the cause of cancers that come back in these long-term survivors”.
The findings, suggest that vaccines based on selected neoantigens could be used as personalised immunotherapy for people with pancreatic cancer, to boost their immune system to attack the tumour and stop the development of these stealth cells.
“These neoantigens don’t drive the cancer themselves, but they do attract immune attention that snuffs out any recurrence of cancer,” says Professor Gill. “This research explains how the cancers in long-term survivors evolve to escape the immune system and points us towards ways to try to stop this happening.”