We know that the immune system influences when cancer occurs and how it progresses. While we understand this process in model systems, such as mice, the relevant mechanisms in humans remain largely unknown. The CENTRI project uses an innovative concept to investigate this problem directly in humans: it monitors the evolution of immune responses over lifespans in Lynch syndrome, a genetic cancer predisposition. Because Lynch syndrome triggers very strong anti-tumour immune responses, we can detect how these defences fail and enable cancer to emerge.
Using samples from people with Lynch syndrome, from different cohorts and clinical trials, CENTRI aims to characterise immune cells, specifically T lymphocytes, during the development of colon tumours. This characterization aims to clarify why the immune system stops protecting patients with Lynch in the long term. In the same way, this information can be used to develop new diagnostic tools for early detection, as well as to identify new therapeutic targets. These discoveries will help us understand how our defences act against other tumours.
The project, funded with 1.8 million euros, will use advanced single-cell sequencing and machine learning methods to identify these complex patterns. It will also explore how the immune system changes after vaccination against Lynch syndrome, a strategy that is being explored as a preventive therapy in the gastroenterology service of the Hospital Clínic. CENTRI will then test whether these changes affect the function of immune cells using animal models carrying the patients' own immune systems.This project is being carried out within the framework of the Clínic Barcelona Comprehensive Cancer Centre.
According to Walle, "Historically, we have studied how the immune system slows down the development of tumours mainly through animal models. CENTRI changes the perspective by studying this process directly in humans. This knowledge will help develop new diagnostic techniques and therapies. My vision is that we can use immune cells as 'sentries' to find those few malignant cells that escape the immune system and give rise to very aggressive tumours."
ERC Starting Grants support research with major potential to advance high-impact scientific knowledge. The ERC is the most prestigious and demanding scientific body in the EU, and this year has been particularly competitive with a grant award rate of just 9%.
This is the fourth consecutive call in which an IDIBAPS staff member has received an ERC Starting Grant. Last year it was awarded to Ferran Nadeu for the CLL-STORY project to reconstruct the biological history of chronic lymphocytic leukaemia. Prior to that, Marianna Spatola received funding for the ImmuBRAIN project, which aims to better understand the immunological mechanisms of autoimmune encephalitis. And in 2023, Silvia Affò was awarded this grant to develop the DynamHet project, which studies the origin, evolution, and function of heterogeneity in cancer-associated fibroblasts.
