Previously Funded Research

Crispin Hiley, MD, PhD

University College London

Research Project:

Determinants of immune age and immune surveillance for early detection

Summary:

Lung cancer is the leading cause of cancer deaths around the world. In the United States alone, nearly 200,000 people are diagnosed each year. Unfortunately, most lung cancers are found at a late stage, when treatments are less effective. Finding lung cancer early—while it is still treatable—is key to saving lives.

Right now, screening programs in the U.S. and U.K. use low-dose CT scans to detect lung cancer in people at high risk, such as older adults with a history of smoking. These programs have helped catch many cancers early, but there are still major challenges. Sometimes CT scans show something that looks suspicious but turns out not to be cancer, leading to unnecessary tests and worry. Other times, cancer is missed. Access to screening is also not equal—people from underserved communities often face more barriers to getting screened. And repeated CT scans raise concerns about radiation exposure, which may increase cancer risk later in life.

Many lung cancers are found by chance when people have imaging done for other reasons, rather than through a formal screening program. Managing these “incidental” lung nodules can be tricky. Some patients don’t get the right follow-up, which can lead to delayed diagnosis and worse outcomes. Blood-based tests, often called “liquid biopsies,” could be a game-changer for early lung cancer detection. These tests look for signs of cancer in the blood, offering a simpler and less invasive option than imaging. However, current liquid biopsy tests—mainly those looking for tumor DNA—don’t always catch cancer early enough. They often detect cancer only after it has started to spread.

The immune system may offer a new way to find cancer sooner. The body’s immune response can change very early in cancer development, even before a tumor becomes detectable. However, as we age, our immune system becomes less effective—a process known as immune aging or immunosenescence—which could partly explain why cancer risk increases with age. Studying how immune aging affects cancer detection could reveal new clues for finding cancer earlier.

Our project builds on the UK NIMBLE study, the first major lung cancer study focused on the immune response. NIMBLE enrolled 500 people with lung nodules found incidentally and collected blood samples for in-depth immune and genetic analysis. Importantly, NIMBLE includes a wide range of participants, including people who have never smoked, making it more representative of real-world patients. Our goal is to develop a new blood test that measures “immune age” and identifies early immune changes along with genetic mutations linked to cancer risk. Using advanced DNA sequencing, we will look for tiny mutations in blood cells and patterns that suggest past exposure to cancer-causing substances like tobacco smoke. At the same time, we will study immune cells for signs of aging and early cancer-related changes.

By combining all of this information—genetic, immune, and aging signals—along with current clinical factors doctors use to assess lung cancer risk from CT scans, such as the size, shape, and edges of lung nodules (for example, nodules with irregular or spiky borders that may be more concerning)—we hope to create a highly sensitive and accurate blood test to detect lung cancer early In the future, we plan to validate this test in other patient groups and work toward making it available in clinical practice. A blood test like this could help doctors decide which lung nodules are cancerous and which are harmless, reducing unnecessary procedures and getting patients the treatment they need faster. Ultimately, this approach could improve survival rates, lower healthcare costs, and help make early cancer detection more accessible for everyone.