Detecting brain tumours through blood-based immune signatures

Gliomas carrying the IDH1 R132H mutation are among the most common primary brain cancers in younger adults, but current diagnostic pathways rely on a biopsy which is an invasive procedure. A collaboration between the Blundell group at our University of Cambridge centre and the Green and Platten groups at our German Cancer Research Centre (DKFZ) centre has provided the first demonstration that a tumour's genetic signature can be read directly from the patient's immune repertoire.

Using data from DKFZ clinical trials of IDH1 R132H peptide vaccination, the team identified T-cell receptors that expand specifically in response to the mutation. These findings were validated against single-cell binding data generated through a specialist immunology platform at the University of Cambridge.

The team scored the peripheral blood repertoires of around 100 glioma patients for validation. IDH1 R132H-specific receptors were significantly enriched only in patients carrying IDH1-mutant tumours.

Building on this result, the collaboration has secured one of two German National Cancer Prevention Center awards (HERALD). More than 4,400 candidate diagnostic T-cell receptors have been cloned at DKFZ, with scale-up studies planned across the next phase.

Immunology

Harnessing the immune system for cancer early detection.

Inequalities

Understanding and addressing cancer inequalities in early detection.

Inherited cancers

Investigating hereditary cancer populations to understand disease initiation and inform early detection and interception strategies.

Interception

Detecting and understanding pre-cancerous changes to identify targets for precision cancer interception.