Exploring the landscape of programmed cell death protein-1 and cluster of differentiation 28 positive T cells and cytokines in non-small cell lung cancer: A retrospective case-control study.

ObjectiveProgrammed cell death protein-1 (PD-1) and cluster of differentiation (CD) 28 (CD28) are representative stimulatory and inhibitory signals that regulate T cell function. This retrospective study aimed to evaluate alterations in peripheral PD-1- and CD28-positive T cell populations in patients with benign pulmonary nodules and non-small cell lung cancer (NSCLC).MethodsKaplan-Meier plotter was used to analyze the prognostic value of PD-1 and CD28 expression in NSCLC. Flow cytometry was used to detect T cell subsets in peripheral blood. Serum tumor markers were detected using a chemiluminescent analyzer. Cytokine levels were detected by Cytometric Bead Array.ResultsA total of 526 patients with NSCLC (early stage: 251; advanced stage: 275), 55 patients with benign pulmonary nodules, and 33 healthy participants were included. Kaplan-Meier plotter analysis showed that higher PD-1 expression was correlated with poorer survival in patients with lung adenocarcinoma), whereas higher CD28 expression was correlated with favorable survival in patients with lung adenocarcinoma and lung squamous cell carcinoma. Compared with healthy controls, the proportion and number of peripheral PD-1+CD3+ T cells and PD-1+CD4+ T cells were significantly increased in patients with benign pulmonary nodules and NSCLS. The numbers of CD28+CD3+ T cells and CD28+CD4+ T cells were lower in patients with NSCLC than in healthy controls. Notably, there were no differences in PD-1+ or CD28+ T cells between patients with benign pulmonary nodules and NSCLC. The numbers of PD-1+ and CD28+ T cells were lower in patients with advanced NSCLC than in those with early NSCLC. Additionally, the levels of serum tumor markers (carcinoembryonic antigen, neuron-specific enolase, cancer antigen 125, cytokeratin 19 fragment antigen 21-1, and cancer antigen 50) were not different between patients with benign pulmonary nodules and early NSCLC but were higher in patients with advanced NSCLC. Moreover, serum interleukin 6 and interferon-γ levels were higher in patients with advanced NSCLC than in those with benign pulmonary nodules and early NSCLC.ConclusionIncreased PD-1 and decreased CD28 suggest potential T cell dysfunction in patients with benign pulmonary nodules and NSCLC. Patients with benign pulmonary nodules showed characteristics similar to those of patients with early NSCLC with respect to PD-1+/CD28+ T cells, tumor markers, and cytokines.