Predicting Response to Checkpoint Inhibitors in BRCA1/2-Deficient Ovarian Cancer
Posted: Monday, May 7, 2018
Tumors that lose the protein phosphatase and tensin homolog (PTEN) seem to be less likely to respond to checkpoint inhibitor therapy than tumors that maintain PTEN levels in BRCA1/2-deficient ovarian cancer, according to research presented by Adam Kraya, PhD, of the University of Pennsylvania, (Penn), Philadelphia, at the 2018 American Association for Cancer Research (AACR) Annual Meeting in Chicago (Abstract 5729).
“This [PTEN loss] is an effect we’ve seen in other disease types like melanoma and leiomyosarcoma, but this is the first study to identify the effect in BRCA-deficient ovarian cancer,” stated senior study author Katherine L. Nathanson, MD, Deputy Director of the Abramson Cancer Center, in a Penn Medicine press release.
The investigators analyzed data from 86 ovarian cancers with germline or somatic mutations in BRCA1/2 from the Cancer Genome Atlas (TCGA, n = 68) and Penn (n = 18). Using genomic analysis and immunohistochemistry, they evaluated the tumors for potential immunosuppressive mechanisms associated with BRCA1/2-deficiency and to establish factors that may determine response to PD-1/PD-L1 inhibitors.
The TCGA cohort analysis found that copy number loss in PTEN was associated with lower levels of cytolytic immune molecules and immune-activating pathways—both measures of immune activity. Also, BRCA1/2-deficient tumors expressed lower levels of co-stimulatory immune factors and counter-regulatory immune inhibitors versus PTEN, suggesting lower immune activity with PTEN loss. In the Penn tumor cohort, lower levels of immune molecules such as CD3, CD8, FoxP3, and PRF-1 were identified with PTEN loss. In short, PTEN loss seemed to correlate with the loss of molecules that can generate an immune response.
