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

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

Affiliations
Comparative Study

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

Han Sol Choi et al. Oncotarget. .

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.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Disease-free and overall survival curves of gastric cancer patients according to the proportions of CD8+ T cells (A, D), regulatory T cells (Tregs) (B, E) and Myeloid derived suppressor cells (MDSCs) (C, F) among total examined cells
Figure 2
Figure 2. Disease-free and overall survival curves of gastric cancer patients according to the proportions of CD8+ T cells among CD3+ T cells (A, D), regulatory T cells (Tregs) among CD4+ T cells (B, E), and Myeloid derived suppressor cells (MDSCs) among CD45+ leukocytes (C, F)
Figure 3
Figure 3. Analysis strategy to detect regulatory T cells (Tregs) and Myeloid derived suppressor cells (MDSCs) in tumor tissues by multicolor flow cytometry
Dot plots of representative patient are displayed. Multiple antibodies were used to sort out the appropriate immune cell lineages among tumor cells. A. Tregs were defined as CD45+CD4+CD25± and FOXP3+. B. MDSCs were defined as CD45+, CD11b+, HLA−DR− and CD14+.

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