The impact of the molecular profile of the tumor microenvironment on the prognosis of NSCLC

Abstract

Purpose The present study was performed to clarify the correlation between macrophages, tumor neo-vessels and programmed cell death-ligand 1 (PD-L1) in the tumor microenvironment (TME) and the clinicopathological features of non-small cell lung cancer (NSCLC) and to explore the prognostic factors of stromal features in NSCLC. Methods Tissue microarrays containing 92 NSCLC patients were studied with immunohistochemistry (IHC). The distribution and quantitative data of CD68- and CD206-positive tumor-associated macrophages (TAMs) in tumor islets and tumor stroma, and the expression of tumor neo‑vessels and PD-L1, were analyzed by inverted microscopy and Image-Pro Plus 6.0 software. Prognostic analyses with the clinicopathological characteristics and tumor microenvironment features were performed. Results The number of CD68-positive macrophages in each location of the tumor islets and tumor stroma was significantly higher than that of CD206-positive macrophages, and they were significantly correlated (P < 0.0001). Survival analysis revealed that CD68- and CD206-positive TAMs in the tumor stroma and tumor islets were significant prognostic factors (P < 0.05, respectively). Comprehensive analysis of CD206-positive stromal TAMs showed that CD105 and PD-L1 were significant prognostic factors (P=0.045). Moreover, CD68-positive TAMs in tumor islets and the expression of PD-L1 were independent predictors of poor prognosis for NSCLC. Conclusion Thus, the key elements in the tumor microenvironment, including tumor neo‑vessels, macrophages and PD-L1, were heterogenic in NSCLC tissues and had significant roles in cancer invasion and metastasis. The combined analysis of key components in the tumor microenvironment was an important prognostic factor.