title: Activation of glioma cells generates immune tolerant NKT cells.
abstract: Therapeutic outcomes of glioma are currently not encouraging. Tumor tolerance plays an important role in the pathogenesis of glioma. It is reported that micro RNAs (miR) are associated with tumor development. This study aims to investigate the role of miR-92a in the development of tolerant natural killer T (NKT) cells. In this study, U87 cells (a human glioma cell line) and primary glioma cells were prepared. The assessment of miR-92a was performed by real time RT-PCR. The expression of interleukin (IL)-10 and IL-6 in NKT cells was evaluated by flow cytometry. Results showed that abundant IL-6(+) IL-10(+) NKT cells were detected in glioma tissue. Cultures of glioma cells and NKT cells induced the expression of IL-6 and IL-10 in NKT cells. Glioma cells expressed miR-92a; the latter played a critical role in the induction of IL-6 and IL-10 expression in NKT cells. The expression of the antitumor molecules, including perforin, Fas ligand, and interferon-γ, was significantly attenuated compared with control NKT cells. The IL-6(+) IL-10(+) NKT cells showed less capability in the induction of apoptosis in glioma cells, but showed the immune suppressor functions on CD8(+) T cell activities. We conclude that glioma-derived miR-92a induces IL-6(+) IL-10(+) NKT cells; this fraction of NKT cells can suppress cytotoxic CD8(+) T cells.
authors.affiliation: From the Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China, and.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wei
authors.affiliation: From the Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China wenhairfan@163.com.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Fan
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D005910:Glioma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D016753:Interleukin-10
keywords: Cellular Immune Response; Glioblastoma; Lymphocyte; RNA; Tolerance