Study has been published in the Journal of the National Cancer Institute (JNCI)
Almac Group’s diagnostics business unit has announced the identification of a novel immune response mechanism in breast tumours deficient in DNA repair.
The JNCI publication, titled ‘Activation of STING-Dependent Innate Immune Signalling By S-Phase-Specific DNA Damage in Breast Cancer,’ follows on from Almac’s previous publication of a 44-gene immune-based assay capable of prospectively identifying breast cancer patients with a defect in the FA/BRCA pathway who benefit from anthracycline based chemotherapy.
The current study explains the molecular basis of this 44-gene immune-based assay and demonstrates that the genes in the assay reflect activation of the innate immune response cGAS/STING/TBK1/IRF3 pathway in response to DNA damage.
The study is particularly interesting because it provides a clear rationale for the observed link between DNA repair deficiency and activation of the immune checkpoint PD-L1. Almac will now pursue their 44-gene assay as a means of prospectively identifying breast cancer patients likely to respond to PD-L1 targeted therapies.
The study was performed in collaboration with Queens University Belfast. Dr Eileen Parkes, Academic Clinical Lecturer at the Centre for Cancer Research and Cell Biology at Queen’s University, said: 'This research provides a new way of explaining how immune cells are targeted to certain breast tumours, and could help decide which patients are most likely to respond to this new class of immune therapies. Approximately one third of breast cancers will have this immune-rich picture, therefore a huge amount of patients could benefit from this research.'
Professor Richard Kennedy, MD, PhD, McClay Professor in Medical Oncology, Queens University Belfast and VP and Medical Director, Almac Diagnostics, commented: 'The study provides strong justification for the underlying biology that causes enhanced PD-L1 expression. Almac will now engage with pharma and academia to investigate the potential clinical benefit for predicting response to immune checkpoint inhibitors, such as PD-L1 and IDO1 and their use in combination with DNA damaging agents.'