The prognostic effects of tumor infiltrating regulatory T cells and myeloid derived suppressor cells assessed by multicolor flow cytometry in gastric cancer patients

Oncotarget. 2016 Feb 16;7(7):7940-51. doi: 10.18632/oncotarget.6958.

Abstract

The prognostic effects of tumor infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs) and myeloid derived suppressing cells (MDSCs) are inconclusive in gastric cancers. We investigated the frequencies of TILs including CD8+ T cells, CD45+CD4+CD25± FOXP3+ Tregs, CD45+CD11b+ CD14+ HLA-DR- MDSCs in 28 gastric cancer tissues by using multicolor flow cytometry. In gastric cancer tissue, the percentage of Tregs among the CD4+ T cell subset was substantially increased compared to that of Tregs among peripheral blood CD4+ T cells from the controls. High frequency of CD8+ T cells among CD3+ T cells correlated with increased overall survival (OS) (p = 0.005). High frequency of Tregs among CD4+ T cells correlated with increased OS (p < 0.001), and disease-free survival (DFS) (p = 0.039) and was an independent prognostic factor in OS (Hazard ratio: 0.047; 95% confidence interval, 0.006-0.372; p = 0.004). High frequency of MDSCs among total examined cells correlated with decreased OS (p = 0.027) and was an independent prognostic factor in OS (Hazard ratio 8.601; 95% confidence interval, 1.240-59.678; p = 0.029). We have demonstrated that high levels of Tregs among tumor-infiltrating CD4+ T cells were favorable, but an increased proportion of MDSCs was an adverse independent prognostic factor in gastric cancer. Our results may provide important insights for future immunotherapy in gastric cancer.

Keywords: gastric cancer; myeloid derived suppressor cells; prognosis; regulatory T cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Combined Modality Therapy
  • Female
  • Flow Cytometry / methods*
  • Follow-Up Studies
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Myeloid-Derived Suppressor Cells / immunology*
  • Myeloid-Derived Suppressor Cells / pathology
  • Neoplasm Recurrence, Local / immunology*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Tumor Cells, Cultured