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

Cancer Med. 2019 Dec;8(17):7330-7344. doi: 10.1002/cam4.2596. Epub 2019 Oct 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology*
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / metabolism
  • Gastrectomy
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / analysis
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Stomach / immunology
  • Stomach / pathology
  • Stomach / surgery
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Microenvironment / immunology


  • Biomarkers, Tumor
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase