Natural killer cell activity as a biomarker for the diagnosis of lung cancer in high-risk patients

Abstract

Objective Natural killer (NK) cells play an essential role in the immune response against cancer. However, immune escape mechanisms may cause inferior NK cell activity (NKA) in patients with cancer. This prospective study examined the relationship between NKA and lung cancer in a high-risk cohort. Methods In a cohort study, 250 participants referred by their general practitioner for suspicion of lung cancer were included. Before clinical investigation, blood was collected into NK Vue tubes, and the level of interferon gamma after 24 hours served as a surrogate marker for NKA. Results Among 250 patients, 79 were diagnosed with lung cancer. No difference in NKA was found between patients with lung cancer and control participants in which lung cancer was ruled out (median 226 pg/mL vs. 450 pg/mL). However, there was a significant difference in NKA between patients with late-stage lung cancer and controls (median 161 pg/mL vs. 450 pg/mL). A linear regression model showed that NKA was not influenced by age, sex or smoking status. Conclusions The significantly lower NKA in patients with late-stage lung cancer warrants further investigation combining NKA with other biomarkers and examining the potential role of NKA as a marker of disseminated disease.

Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients

“…However, NK cells also play a key role in preventing tumor progression and metastasis through their direct cytotoxic activity and secreted cytokines [ 47 ]. Recent studies have shown that low NKA is significantly associated with a higher risk of various cancers, such as hepatocellular carcinoma [ 36 ], colorectal cancer [ 48 ], head and neck squamous cell carcinoma [ 49 ], lung cancer [ 50 ], and pancreatic cancer [ 51 ]. Jun’s study showed that NKA is progressively impaired during tumor development, and its dysfunction is associated with recurrence and survival outcomes [ 52 ].…”

Early Detection of Lung Cancer: Biomarkers and CT Scans

“…Natural killer cell activity was measured in whole blood using the NK Vue ® assay (NKMAX Co Ltd, Seongnam-si, South Korea) that consists of a special sample tube and an ELISA. The analyses were performed at the Department of Clinical Biochemistry, Lillebaelt Hospital Vejle -University Hospital of Southern Denmark, Denmark and has been described previously (82). Besides Na-heparin as the anticoagulant, the NK Vue ® tubes hold an NK cell-stimulating agent, Promoca ® .…”

“…When applying the USPSTF screening criteria, detection of stage I-II vs. stage III-IV were equally low, with AUC values of 0.62 and 0.61, respectively. The ability of NKA to detect all-stage lung cancer and late-stage lung cancer was assessed using ROC curves (Figure 12) (82). The AUC for detecting any stage of lung cancer was 0.57 (95% CI: 0.49-0.66), while the AUC for detecting late-stage lung cancer was 0.66 (95% CI: 0.57-0.75).…”

“…Next, the importance of clinical factors, such as age, sex and smoking status on NKA was assessed using a multiple linear regression model (82). The results are presented in Table 5 and do not find NKA to be influenced by the above-mentioned factors.…”

“…Study 3 evaluated whether the activity of NK cells was downregulated in patients with lung cancer from the DETECT high-risk cohort, and whether this was sufficient and robust enough to be used as a diagnostic tool (82). No significant difference was seen when comparing NKA of patients with lung cancer (any stage) with control subjects, and the ROC curve yielded an AUC value of 0.57.…”