Immunotherapy using
immune checkpoint inhibitors has demonstrated durable responses and has significantly improved survival in patients with
non-small cell lung cancer (NSCLC). Moreover,
immunotherapy is increasingly used in combination with cytotoxic treatments such as
chemotherapy and
radiotherapy. Although the combined treatments are more effective, the underling mechanisms that lead to higher antitumor activity are not fully understood. Therefore, the aim of the current retrospective study was to determine the relationship between expression of immune checkpoints [
programmed cell death protein 1 (PD-1) and
programmed death-ligand 1 (PD-L1)] and the
enzyme DNA-dependent protein kinase (
DNA-PK), which is part of a key pathway involved in the repair of cytotoxic
cancer therapy induced damage. Surgically excised NSCLC tissues (n=121) were histologically examined for overall extent of
inflammation (score 0-3). Expression levels of PD-1 (number of PD-1 positive cells), PD-L1 [
tumor proportion score (TPS); %] and
DNA-PK (proportion of
DNA-PK positive
tumor cells; %) were determined using immunohistochemistry. Expressions of these markers were compared in different clinicopathological subgroups and later used for nonparametric Spearman correlation analysis to determine associations. In patients with NSCLC, PD-1 was significantly expressed in males (P=0.030) and in patients with no or trivial
inflammation scores (P=0.030). PD-L1 expression was also significantly higher in current smokers (P=0.025). Correlation analysis was based on the individual values of patients and revealed a significant association between one of the targets of
immune checkpoint inhibitors and
tumor cell
DNA-PK.
Tumors with higher numbers of PD-1 positive cells also demonstrated higher
tumor cell
DNA-PK expressions (P=0.027). The results demonstrated a significant positive correlation between the PD-1/PD-L1 axis and
tumor cell
DNA-PK expression in patients with NSCLC. Further studies are required to clarify the significance of this correlation and its effect on the efficacy of
immunotherapy and cytotoxic
cancer therapy combinations.