Schematic of matched scRNA-seq and scTCR-seq of CD4+ T cells from paired PBMC and HGLs. Credit: Nature (2026). DOI: 10.1038/s41586-026-11066-6

A 'rising fog' may cloud the immune system's ability to detect tumors and may be the key to tackling lung cancer that is developing years before diagnosis. The team at University College London (UCL) followed this signal using prototype blood tests and reversed it using drugs.

Led by associate professor James Reading and professor Sam Janes, the study published in Nature potentially opens up new ways to intercept the disease in its early, precancerous stages.

Early intervention

There are around 32,800 lung cancer deaths in the U.K. every year. Only about 1 in 10 (11.1%) people diagnosed with lung cancer are predicted to survive for 10 years or more. By the time the disease causes noticeable symptoms, and in cases of advanced cancer, it is harder to treat.

Reading, an associate professor at UCL, 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 tumors 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 analyzed similar processes in mice to understand what makes precursors of lung cancer (called precancers or lesions) develop into full-fledged tumors.

They discovered that regulatory T cells (Tregs), a set of specialized cells that form part of the immune system, gradually built up months or years before cancer developed.

Tregs typically hold back other cells, pausing their activity, which could be allowing precancers 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 Treg 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 Tregs' immune-suppressing effect.

This approach halved the proportion of animals that developed lung tumors in laboratory experiments and prevented the formation of all large tumors.

Dr. Charlotte Durkin, associate director of molecular and cellular medicine at MRC, 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."

Cancer interception

Janes, interim dean of the Faculty of Population Health Sciences at UCL, said, "We're moving from largely treating cancer when it develops toward tackling the precancerous disease. This is called cancer interception, an exciting and emerging area of research which we hope will stop some precancers from ever becoming cancers in the first place."

Dr. Catherine Elliott, director of research and partnerships at Cancer Research UK, said, "This work is helping lay the foundations for more personalized approaches to cancer prevention, detection and interception. It's an important step toward understanding the interaction between the immune system and the development of lung cancer, and ultimately how we might stop cancer before it starts."

More information: Samuel Gamble et al, A preinvasive regulatory T cell axis for lung cancer interception, Nature (2026). DOI: 10.1038/s41586-026-11066-6

Provided by Medical Research Council

Source: MedicalXpress

Original article: https://medicalxpress.com/news/2026-10-immune-fog-flag-lung-cancer.html