High transforming growth factor β expression represents an important prognostic parameter for surgically resected...

The tumor microenvironment comprises various cellular components and associated subcellular molecules with antitumor and protumor effects. Because respective targeted treatment strategies are arising, it is important to characterize the exact role of these parameters. This study provides a comprehensive analysis of key immunologic factors in the tumor microenvironment of 383 surgically resected non-small cell lung cancer specimens. CD4, CD8, forkhead box protein P3, transforming growth factor β, Casitas B-cell lymphoma-b, programed death 1, T-cell-restricted intracellular antigen 1, granzyme B, mast cell tryptase, and stromal cell-derived factor 1 were analyzed by immunohistochemistry using a standardized tissue microarray platform. Extensive clinical data enabled detailed clinicopathologic correlations over a postoperative follow-up period of 15 years. Among the immunologic variables focused on, transforming growth factor β expression was the only prognostically relevant factor. Transforming growth factor β was more frequently expressed in adenocarcinoma as compared with other histologic subtypes. Expression of transforming growth factor β in tumor-infiltrating lymphocytes or in tumor cells was associated with significantly reduced postoperative survival time especially in patients with squamous cell carcinoma (P = .035 and P = .046, respectively). In these patients, the amount of transforming growth factor β-positive tumor-infiltrating lymphocytes represented the only independent immunologic parameter with prognostic significance by multivariat analysis (P = .021; hazard ratio, 2.602; 95% confidence interval, 1.159-5.844). These results should help to identify patients who are most suitable for therapeutic strategies aiming to block the transforming growth factor β signaling pathway.