Open Access Research

Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma

Jiang Li13*, Zhou-Feng Huang13, Geng Xiong1, Hao-Yuan Mo2, Fang Qiu2, Hai-Qiang Mai2, Qiu-Yan Chen2, Jia He3, Shu-peng Chen1, Li-Min Zheng13, Chao-Nan Qian2 and Yi-Xin Zeng1

Author Affiliations

1 State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China

2 Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, China

3 Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China

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Journal of Translational Medicine 2011, 9:189  doi:10.1186/1479-5876-9-189

Published: 4 November 2011

Abstract

Background

CD8+ effector cells often have an antitumor function in patients with cancer. However, CD8+Foxp3+ regulatory T cells (Tcregs) and interleukin (IL)-17-producing CD8+ T cells (Tc17 cells) also derive from the CD8+ T cell lineage. Their role in the antitumor response remains largely unknown. In the present study, we aimed to investigate the distribution, characterization, and generation of CD8+ Tcregs and Tc17 cells in NPC patients.

Methods

Peripheral blood and tumor biopsy tissues from 21 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were collected, along with peripheral blood from 21 healthy donors. The biological characteristics of Tcregs and Tc17 cells from blood and tumor tissues were examined by intracellular staining, tetramer staining and fluorescence-activated cell sorting (FACS) analysis. The suppressive function of Tcregs was investigated using a proliferation assay that involved co-culture of sorted CD8+CD25+ T cells with naïve CD4+ T cells in vitro.

Results

We observed an increased prevalence of Tcregs and Tc17 cells among tumor-infiltrating lymphocytes (TILs) and different distribution among peripheral blood mononuclear cells (PBMCs) in NPC patients. Cytokine profiles showed that the Tcregs expressed a high level of IL-10 and low level of transforming growth factor β, whereas Tc17 cells expressed a high level of tumor necrosis factor α. Interestingly, both subsets expressed a high level of interferon γ in TILs, and the Tcregs suppressed naïve CD4+ T cell proliferation by a cell contact-dependent mechanism in vitro. Moreover, we demonstrated the existence of Epstein-Barr virus latent membrane protein (LMP) 1 and LMP2 antigen-specific Tcregs in NPC.

Conclusions

Our data provide new insights into the composition and function of CD8+ T-cell subsets in NPC, which may have an important influence on NPC immunotherapy.

Keywords:
Nasopharyngeal carcinoma; Tumor-infiltrating lymphocytes; CD8+ regulatory T cells (Tcreg); IL-17-producing CD8+ T cells (Tc17)