A scientist from the Francis Crick Institute has made a groundbreaking discovery in understanding how the genetic complexity of tumours can be recognised and exploited by the immune system, even when the disease is at its most advanced stages.
Professor Charles Swanton, from the Crick, jointly led the research with Dr Sergio Quezada, head of the Immune Regulation and Cancer Immunotherapy lab at the UCL Cancer Institute.
The research, published in Science on Thursday, could guide future immunotherapies and improve the way existing immunotherapy drugs are used.
As a tumour develops, the diversity of its genetic faults can be flagged on the cancer cell surface, as unique mutations appear in different parts of the tumour.
Crucially, by analysing data from hundreds of patients from previous studies, researchers found that some of these flags - known as antigens - represent the very earliest mutations of the disease and are displayed on all cells in the tumour, rather than a subset of tumour cells.
Then, in the lab, they isolated specialised immune cells, called T-cells, from samples of two patients with lung cancer that can recognise these common flags present on every tumour cell.
Although they have the potential to wipe out all cancerous cells within the tumour, these potent immune cells are switched off by the tumour's defences.
This research paves the way for therapies that specifically activate these T cells to target all the tumour cells at once based on the disease's genetic signature. In the future, scientists could exploit this by developing a therapeutic vaccine to activate T-cells, or harvesting, growing and administering T-cells back into the patient that recognise the antigens common to every cancer cell.
Professor Charles Swanton said: "This is exciting. There was evidence that complex tumours with many mutations could increase the chance of the immune system spotting them; now we can prioritise and target tumour antigens that are present in every cell, the Achilles heel of these highly complex cancers.
"This opens up a way to look at individual patients' tumours and profile all the antigen variations to figure out the best ways for immunotherapy treatments to work, prioritising antigens present in every tumour cell and identifying the body's immune T cells that recognise them. This is really fascinating, and takes personalised medicine to its absolute limit where each patient would have a unique, bespoke treatment."
Dr Quezada added: "For many years we have studied how the immune response to cancer is regulated without a clear understanding of what it is that immune cells recognise on cancerous cells. Based on these new findings, we will be able to tell the immune system how to specifically recognise and attack tumours."
The research was funded by Cancer Research UK and the Rosetrees Trust.
