Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non‐small cell lung cancer

BACKGROUND: The establishment of biomarkers that can be used to predict the response to immunotherapy for malignancy is extremely important. In particular, noninvasive analysis of immune cells from peripheral blood before treatment has gained increased attention, and natural killer (NK) cell activity has been shown to be related to treatment response. Here, we aimed to confirm the relationship between the response to immunotherapy and NK cell activity. METHODS: In this prospective observational study, patients with advanced NSCLC who were scheduled for immunotherapy from October 2018 to December 2019 were enrolled. Baseline NK cell activity was compared according to the best clinical response to immunotherapy. RESULTS: A total of 54 patients with advanced NSCLC were enrolled, and 34 patients were analyzed. The baseline NK cell activity was significantly higher in the non‐PD group than in the PD group (P = 0.002). At the cutoff level of ≥1200 pg/mL, baseline NK cell activity yielded a sensitivity of 80% and a specificity of 68.4% in predicting the response to immunotherapy (AUC = 0.8, P < 0.003). The median progression‐free survival (PFS) was significantly better in the high NK group (P = 0.003), and correlation between baseline NK cell activity and PFS was also confirmed (r = 0.517, P = 0.002). CONCLUSIONS: Baseline NK cell activity was related to the response to immunotherapy and the PFS. We suggest that NK cell activity from peripheral blood before immunotherapy is a noninvasive, simple, and novel way to predicting the treatment response in patients with NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The response to immunotherapy was significantly better in patients with high baseline NK cell activity, and there was a significant correlation between baseline NK cell activity and PFS. What this study adds: This study demonstrates the efficacy of baseline NK cell activity from peripheral blood as a biomarker for predicting immunotherapy response.