The Prognostic value of intratumoral expression of IL-17A+CD4+, CD4+ and CD8+ T cells in non-small cell lung cancer

Abstract

Introduction: Immune responses within the tumor microenvironment are increasingly implicated as determining factor in tumor progression and aggressiveness. Different subsets of tumor infiltrating T lymphocytes are believed to play essential role in the immune response to cancer cells. Study aim was to investigate T cells (IL-17A+CD4+, CD4+ and CD8+) distribution in NSCLC and to determine the prognostic significance of these cells in NSCLC patients. Methods: We analyzed lung tissue specimens from 80 newly diagnosed and untreated patients who underwent surgery for NSCLC (stages I–III), and 16 control group subjects, who underwent surgery due to recurrent spontaneous pneumothorax. Slides were immunohistochemically analyzed for the expression of IL-17A+CD4+, CD4+ and CD8+ T cells. Quantitative evaluation of these cells was done in 10 most representative high-power fields (HPFs ×400 magnification) per tissue section. The number of cells with positive staining was counted manually in two locations: tumor stroma and tumor islets. Results: Greater amount of IL-17A+CD4+, CD4+ and CD8+ T cells was found in NSCLC tumor tissue comparing with control group patients (24 [12-47] vs. 4 [2-6], respectively P<0.001; 153 [53-348] vs. 26.5 [18-37] P<0.001 and 166.5 [57-307] vs. 60 [39-115], P<0.001). Predominant infiltration of IL- 17A+CD4+, CD4+ and CD8+ T cells was found in tumor stroma compared to tumor islets (P<0.001). Based on univariate stage, pT status, lymph node status, CD4+/CD8+ ratio, total number of tumor infiltrating IL-17A+CD4+ were predictors for OS. A multivariate analysis revealed that total number of tumor infiltrating IL-17A+CD4+ was an independent prognostic factor of reduced survival (HR (95%CI) = 0.31 (0.13-0.77); P < 0.05). Conclusions: Our study demonstrated that increased total number of tumor infiltrating IL-17A+CD4+ is associated with reduced NSCLC patients’ survival.