NK cell activity and methylated HOXA9 circulating tumor DNA as prognostic biomarkers in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Background: PD-1/PD-L1 inhibitors have improved survival for patients with non-small cell lung cancer (NSCLC), but better prognostic biomarkers are needed. Methods: We prospectively collected plasma from 82 patients with NSCLC before initiating treatment with PD-1/PD-L1 inhibitors and before treatment cycles 2-4. We used the NK Vue assay to measure interferon gamma (IFNγ) as a surrogate for natural killer cell activity (NKA) with a cutoff of 250 pg/mL. Circulating tumor DNA (ctDNA) in the form of methylated HOXA9 was measured by droplet digital PCR. ctDNA status was classified as detectable or undetectable ctDNA. Results: Patients were classified into three groups according to IFNγ levels at the available time points. The NKA-low group had a persistently low level of IFNγ or dropped to and remained at a low level after baseline (