CD4/CD8 + T cells, DC subsets, Foxp3, and IDO expression are predictive indictors of gastric cancer prognosis

Abstract

Abstract Background The tumor microenvironment represents an abnormal niche containing numerous factors, such as T cells, dendritic cells (DCs), regulatory T cells (Tregs), and indoleamine 2,3‐dioxygenase (IDO), involved in maintaining immune homeostasis and tolerance. All these factors may influence the choice of therapy and the clinical outcomes. Methods Flow cytometry was performed to identify CD4+/CD8 + T cells and DCs, and immunohistochemistry was used to evaluate IDO and Forkhead Box P3 (Foxp3) expression; these experiments were performed in order to explore the clinical and prognostic significance of CD4/CD8 + T cells, DCs, Tregs, and IDO expression in gastric carcinoma. Results Smaller tumor size was correlated with higher expression levels of peripheral CD4 + T cells (P = .003) and CD8 + T cells (P = .002), and lower IDO expression (P = .044) in tumors. Well‐differentiated gastric carcinomas displayed higher peripheral (P = .029) and tumor‐infiltrating CD4 + T cell (P = .009) populations and a higher tumor‐infiltrating DC1/DC2 ratio (P = .048). Gastric cancer in the early T stages exhibited higher populations of peripheral DC2s (P = .044) and a higher tumor‐infiltrating DC1/DC2 ratio (P = .012). Gastric cancer at the N0 stage had lower tumor‐infiltrating DC2s (P = .032) and a higher DC1/DC2 ratio (P = .037). IDO expression was positively correlated with tumor‐infiltrating Foxp3 + Tregs (P < .001) as well as DC2s (P < .001), whereas it was negatively correlated with the tumor‐infiltrating CD4/CD8 + T cell ratio (P = .023). Tumor‐infiltrating Foxp3 + Treg was positively correlated with tumor‐infiltrating DC2s (r2 = 0.772; P < .001). At T, N, and TNM stages, the expression levels of peripheral DC2s, tumor‐infiltrating DC1/DC2 ratios, Foxp3 + Tregs, and IDO were significantly correlated with prognosis (P < .05). The T stage and peripheral DC2s were significant risk factors for overall survival. Conclusion Immunocompetent cells and humoral immune factors, including DC2s, CD4+/CD8 + T cells, Foxp3 + Tregs, and IDO, interact with each other to compose a complex community of tumor immune microenvironment, ultimately affecting tumor progression and survival of gastric cancer.

Keywords

• dendritic cell
• gastric cancer
• indoleamine 2,3‐dioxygenase
• regulator T cell