The team at University College London (UCL), funded by Cancer Research UK and the Medical Research Council (MRC), followed this signal using prototype blood tests and reversed it using drugs.
Led by Associate Professor James Reading and Professor Sam Janes, this study potentially opens up new ways to intercept the disease in its early, pre-cancerous stages.
Early intervention
The research, published today in the journal Nature, adds to growing evidence that one day cancer could be targeted before it even develops.
By the time the disease causes noticeable symptoms, and in cases of advanced cancer, it is harder to treat.
There are around 32,800 lung cancer deaths in the UK every year.
Only around one in 10 (11.1%) people diagnosed with lung cancer are predicted to survive for 10 years or more.
Urgent prevention needed
Associate Professor at UCL, Dr James Reading, said:
We urgently need new ways to prevent lung cancer in people at high-risk of developing the disease.
There was a moment when multiple members of my team were telling me that they’d spotted the same unusual regulatory T cell activity.
What excited us most was that these cells weren’t just signaling that cancer might be developing: It was also possible to target this immune fog to intervene and stop tumours from forming, which could give us new ways to prevent lung cancer.
Understanding the precursors of cancer
The team, carefully studied blood and tissue samples collected from people taking part in long-running lung cancer surveillance and screening studies.
They also analysed similar processes in mice, to understand what makes precursors of lung cancer (called pre-cancers or lesions) develop into fully-fledged tumours.
They discovered regulatory T cells (Tregs), a set of specialised cells that form part of the immune system, were gradually building up months or years before cancer develops.
Tregs typically hold back other cells, pausing their activity, which could be allowing pre-cancers to slip through the cracks and develop into lung cancer unchallenged by the immune system.
Identifying people at risk
Using prototype blood tests, the team found that monitoring the Tregs levels could help identify people at increasing risk of lung cancer or patients with an early form of it.
They also explored using targeted cancer drugs to reverse and disperse the Treg ‘fog’ and found that a drug targeting specific immune processes could reverse the Treg’s immune-suppressing effect.
This approach halved the proportion of animals that developed lung tumours in laboratory experiments, and preventing formation of all large tumours.
Discovery science
Associate Director of Molecular and Cellular Medicine at MRC, Dr Charlotte Durkin, said:
This study provides valuable new insight into the early stages of lung cancer development.
By identifying mechanisms that could both signal increased risk and offer opportunities for intervention, this research highlights the potential of discovery science to underpin new approaches to cancer prevention and early detection.
Additional support was also provided by the National Institute for Health and Care Research and other funding partners.
Cancer interception
Interim Dean of the Faculty of Population Health Sciences at UCL, Professor Sam Janes, said:
We’re moving from largely treating cancer when it develops towards tackling the pre-cancerous disease.
This is called cancer interception, an exciting and emerging area of research which we hope will stop some pre-cancers from ever becoming cancers in the first place.
Tailored approach
Director of Research and Partnerships at Cancer Research UK, Dr Catherine Elliott, said:
This work is helping lay the foundations for more personalised approaches to cancer prevention, detection and interception.
It’s an important step towards understanding the interaction between the immune system and lung cancer developing, and ultimately how we might stop cancer before it starts.
The paper is titled ‘A preinvasive regulatory T cell axis for lung cancer interception’.
