BRCA mutations reshape the immune landscape of lung tumours
People with certain cancer-linked gene mutations sometimes respond better to immunotherapy. New research explains why: faults in two well-known genes dramatically alter the environment surrounding a tumour.
BRCA1 and BRCA2 are best known for their role in breast cancer, but they are also active in lung cancer. And what they do inside a cell has major consequences for how the immune system responds to a tumour. The researchers, publishing in eLife, analysed lung adenocarcinoma (a type of lung cancer arising from glandular tissue) using single-cell sequencing, a technique that maps the activity of individual cells.
BRCA1 and BRCA2 are involved in repairing double-strand DNA breaks through a process called homologous recombination. When that repair fails, DNA damage accumulates. This makes cells unstable, but it also attracts the attention of immune cells.
The tumour microenvironment as a battleground
Surrounding every tumour is a complex network of cells and signals called the tumour microenvironment. This environment partly determines whether immune cells can attack the tumour or are blocked from doing so. In BRCA1/2-mutated tumours, the composition and behaviour of T cells within this environment change. T cells are the immune cells capable of directly killing tumour cells.
The study identifies specific transcriptional programmes: patterns of gene activity that differ between BRCA-mutated tumours and those without such mutations. These patterns influence how active T cells are and how well they recognise the tumour.
Why this matters for immunotherapy
Immunotherapy helps the body’s own immune system detect and attack cancer cells more effectively. Its effectiveness varies considerably between patients. This research provides a molecular explanation for why BRCA1/2 mutations in lung cancer correlate with better immunotherapy responses. That could help clinicians select patients most likely to benefit from this treatment.
From a longevity perspective, lung cancer is one of the most common age-related cancers, and better patient selection translates directly into improved survival.