title: Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma.
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.
authors: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China. lijiang2@mail.sysu.edu.cn
authors: Jiang
authors: J
authors: Li
authors: Zhou-Feng
authors: ZF
authors: Huang
authors: Geng
authors: G
authors: Xiong
authors: Hao-Yuan
authors: HY
authors: Mo
authors: Fang
authors: F
authors: Qiu
authors: Hai-Qiang
authors: HQ
authors: Mai
authors: Qiu-Yan
authors: QY
authors: Chen
authors: Jia
authors: J
authors: He
authors: Shu-Peng
authors: SP
authors: Chen
authors: Li-Min
authors: LM
authors: Zheng
authors: Chao-Nan
authors: CN
authors: Qian
authors: Yi-Xin
authors: YX
authors: Zeng
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002277:Carcinoma; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D014763:Viral Matrix Proteins