Circulating Natural Killer Cells as Prognostic Value for Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Correlation with Sarcopenia

SIMPLE SUMMARY: In this study, we provide a basal and longitudinal evaluation of immune cells in advanced non-small-cell lung cancer (NSCLC) patients undergoing PD-1 or PD-L1 blockade. We aimed to explore if any data could be predictive of better outcomes and long-term survival and to detect eventual connections among immune cell subsets and sarcopenia, another known risk factor for progression disease (PD). We found that natural killer (NK) cell basal levels are higher in patients with disease control (DC) compared to PD patients; higher NK cell basal levels predict a longer overall survival (OS); lower NK values represent a risk factor for PD; and after three months of immune check-point inhibitors (ICIs) treatment, NK cells (and the subclass CD56(bright)) significantly increase in DC patients. Interestingly, sarcopenic patients show lower NK cell values at basal levels. ABSTRACT: Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of tumors. Natural killer (NK) cells can play an important role in cancer immune surveillance. The aim of this prospective observational study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICIs in order to identify predictive factors for better survival outcomes. Methods: Forty-seven stage IV NSCLC patients were enrolled. Patients underwent baseline (T(0)) and longitudinal (T(1)) evaluations after ICIs. Peripheral immune blood cell counts were analyzed using flow cytometry. Results: Basal levels of CD3(−)CD56(+) NK cells were higher in patients with controlled disease (DC) compared to progression disease (PD) patients (127 cells/µL vs. 27.8 cells/µL, p < 0.001). Lower NK cell values were independent prognostic factors for shorter overall survival (OS) (HR 0.992; 95% CI 0.987–0.997, p < 0.001) and progression-free survival (PFS) (HR 0.988; 95% CI 0.981–0.994, p < 0.001). During the longitudinal evaluation, CD3(−)CD56(+) NK cells (138.1 cells/µL vs. 127 cells/µL, p = 0.025) and CD56(bright) NK cells (27.4 cells/µL vs. 18.1 cells/µL, p = 0.034) significantly increased in the DC group. Finally, lower values of CD3(−)CD56(+) NK cells (28.3 cells/µL vs. 114.6 cells/µL, p = 0.004) and CD56(dim) NK cells (13.2 cells/µL vs. 89.4 cells/µL, p < 0.001) were found in sarcopenic patients compared to patients without sarcopenia. Conclusions: Peripheral NK cells could represent a non-invasive and useful tool to predict ICI therapy response in NSCLC patients, and the association of low NK cell levels with sarcopenia deserves even more attention in clinical evaluation.