Infiltration of CD8⁺ FOXP3⁺ T cells, CD8⁺ T cells, and FOXP3⁺ T cells in non-small cell lung cancer microenvironment

Background: Studies about CD8⁺ FOXP3⁺ T cells as a subtype of regulatory T cells (Treg cells) in non-small cell lung cancer (NSCLC) are few. Associations among the clinicopathologic factors of NSCLC and tumor-infiltrating lymphocytes (TILs) such as CD8⁺ FOXP3⁺ T cells, CD8⁺ T cells, FOXP3⁺ T cells and tumor PD-L1 expression are unclear.

Methods: We retrospectively enrolled 192 patients who underwent resections for NSCLC. We used tissue microarrays (TMA) with multiplex immunofluorescence and immunohistochemistry staining to evaluate the expression of CD8, FOXP3, cytokeratin, DAPI and PD-L1. We then used Wilcoxon test, Kaplan-Meier method, and Cox hazard proportion model to analyze their relationships with clinicopathologic factors and prognosis.

Results: Density of tumor CD8⁺ FOXP3⁺ T cells was significant by univariate analysis, and positively associated with tumor CD8⁺ T cells and FOXP3⁺ T cells. Density of tumor CD8⁺ T cells was higher in lung adenocarcinoma (LUAD) than squamous cell carcinoma (LUSC), and was an independent prognostic factor for NSCLC. The density of tumor FOXP3⁺ T cells decreased with tumor size. Tumor PD-L1 expression was higher in LUSC than LUAD. Cox hazard proportion model analysis correlated being younger than 65 years, early TNM stage, early T stage, high tumor CD8⁺ T cell density, and adjuvant chemotherapy with longer overall survival.

Conclusion: Infiltration of CD8⁺ FOXP3⁺ T cells, CD8⁺ T cells, and FOXP3⁺ T cells is important in non-small cell lung cancer microenvironment, and needs to be investigated more.