The prognostic significance of PD-1 and its ligands in non-small cell lung cancer

Background: In this study, we aimed to investigate the prognostic value of programmed cell death protein 1 (PD -1), programmed cell death ligand 1 (PD -L1), and programmed cell death ligand 2 (PD -L2) expressions on immune and cancer cells in terms of survival in patients with lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Methods: Between January 2000 and December 2012, a total of 191 patients (172 males, 19 females; mean age: 60.3 +/- 8.4 years; range, 38 to 78 years) who were diagnosed with non -small cell lung cancer and underwent anatomic resection and mediastinal lymph node dissection were retrospectively analyzed. The patients were evaluated in three groups including lung squamous cell carcinoma (n=61), adenocarcinoma (n=66), and large -cell carcinoma (n=64). The survival rates of all three groups were compared in terms of immunohistochemical expression levels of PD -1, PD -L1, and PD -L2. Results: The mean follow-up was 71.8 +/- 47.9 months. In all histological subtypes, PD -1 expressions on tumor and immune cells were observed in 33% (61/191) and in 53.1% (102/191) of the patients, respectively. Higher expression levels of PD -L1 and PD -L2 at any intensity on tumor and immune cells were defined only in lung adenocarcinomas, and PD -L1 and PD -L2 values were detected in 36.4% (22/64) of these patients. The PD -L1 expressions on tumor and immune cells were observed in 41.7% (10/24) and 25% (6/24) of the patients, respectively. The PD -L2 expressions on tumor and immune cells were detected in 16.7% (4/24) and 8.4% (2/24) of the patients, respectively. Univariate and multivariate analyses revealed that PD -1 expression in tumor cells was an independent prognostic factor in all histological subtypes. Conclusion: Our study results suggest that PD -1 expression is a poor prognostic factor for overall survival in patients with completely resected adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.