The dynamics of natural killer cell activity as a prognostic factor in patients receiving curative surgery for non-small cell lung cancer

<bold>Background:</bold> Curative surgery is the preferred treatment for non-small cell lung cancer (NSCLC). However, about 50% of cases recur, which could be linked to the immune function. <bold>Objective:</bold> To evaluate the prognostic impact of dynamic natural killer cell activity (NKA) after curative surgery for NSCLC. <bold>Methods:</bold> We enrolled 95 patients, who underwent curative surgery for NSCLC. Blood was sampled pre-surgery, and at median 4 weeks and 3 months post-surgery, respectively. NKA was measured using the NK Vue® kit. Whole blood was stimulated using a recombinant protein for 24 hours. The level of interferon gamma (IFNγ) in the plasma was measured by ELISA as a surrogate for NKA. IFNγ<250 pg/ml was considered abnormal according to the manufacturer. <bold>Results:</bold> Patients were grouped according to the dynamics of NKA. The NKA-low group (n=17) had IFNγ<250 pg/ml at all available time-points, and the NKA-high group (n=78) had IFNγ≥250 pg/ml at one or more time-points. The NKA-low group demonstrated significantly poorer outcome in landmark analysis of 2-year overall survival (OS, p=0.008) but not recurrence-free survival (RFS, p=0.134). This trend persisted over the total follow-up time (median follow-up 46 months, median survival not reached), with the NKA-low group still exhibiting significantly lower OS (p=0.0484) but not RFS (p>0.05), corresponding to a hazard ratio of 2.507 (95% confidence interval 1.161-5.414, p=0.019) in a multiple Cox regression model adjusting for performance status and stage. <bold>Conclusion:</bold> Dynamic measurement of NKA can identify a group of patients with a poor prognosis, who may benefit from immunomodulating adjuvant or neoadjuvant treatment.