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Article

The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma

  • Authors:
    • Min Ruan
    • Katherine Thorn
    • Shengwen Liu
    • Siyi Li
    • Wenjun Yang
    • Chunye Zhang
    • Chenping Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, P.R. China , Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA, Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, P.R. China
  • Pages: 2103-2110
    |
    Published online on: March 21, 2014
       https://doi.org/10.3892/ijo.2014.2356
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Abstract

Increasing evidence suggests that communication between tumor and immune cells can alter the tumor microenvironment in ways that promote tumor development. The purpose of this study was to characterize the immune response elicited by TLR-9-activated OSCC cells, to identify the cytokines involved in the signaling pathway and to elucidate the molecular mechanism of this pathway in OSCC cells. MTS, flow cytometry and ELISA assay were used to evaluate T-cell immune responses, cancer cell proliferation and pro-inflammatory cytokine secretion, respectively. Western blot analysis, EMSA and ChIP assay were employed to detect the activity of the NF-κB and AP-1 signaling pathways. A marked response was observed when T-cells were co-cultured with supernatants from CpG-ODN-treated OSCC cells. This response was characterized by increased CD4+ and CD8+ T-cell proliferation and an increase in IFN-γ production by the CD4+ T-cell population. Treatment of OSCC cells with CpG-ODN resulted in an increase in IL-6 secretion as well as an increase in AP-1 binding activity to the IL-6 promoter. Moreover, blockage of the TLR-9/AP-1 pathway significantly decreased IL-6 expression and T-cell immune response. In human OSCC, the TLR-9 pathway, when stimulated by CpG-ODNs, promotes a T-cell immune response mediated by AP-1-activated IL-6 secretion. Although the complete molecular mechanism has yet to be understood, these findings provide evidence linking tumor cell activities to immune system responses. In addition, the TLR-9/AP-1/IL-6 pathway provides new therapeutic targets for the prevention and treatment of OSCC.
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Copy and paste a formatted citation
Spandidos Publications style
Ruan M, Thorn K, Liu S, Li S, Yang W, Zhang C and Zhang C: The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma. Int J Oncol 44: 2103-2110, 2014.
APA
Ruan, M., Thorn, K., Liu, S., Li, S., Yang, W., Zhang, C., & Zhang, C. (2014). The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma. International Journal of Oncology, 44, 2103-2110. https://doi.org/10.3892/ijo.2014.2356
MLA
Ruan, M., Thorn, K., Liu, S., Li, S., Yang, W., Zhang, C., Zhang, C."The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma". International Journal of Oncology 44.6 (2014): 2103-2110.
Chicago
Ruan, M., Thorn, K., Liu, S., Li, S., Yang, W., Zhang, C., Zhang, C."The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma". International Journal of Oncology 44, no. 6 (2014): 2103-2110. https://doi.org/10.3892/ijo.2014.2356
Copy and paste a formatted citation
x
Spandidos Publications style
Ruan M, Thorn K, Liu S, Li S, Yang W, Zhang C and Zhang C: The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma. Int J Oncol 44: 2103-2110, 2014.
APA
Ruan, M., Thorn, K., Liu, S., Li, S., Yang, W., Zhang, C., & Zhang, C. (2014). The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma. International Journal of Oncology, 44, 2103-2110. https://doi.org/10.3892/ijo.2014.2356
MLA
Ruan, M., Thorn, K., Liu, S., Li, S., Yang, W., Zhang, C., Zhang, C."The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma". International Journal of Oncology 44.6 (2014): 2103-2110.
Chicago
Ruan, M., Thorn, K., Liu, S., Li, S., Yang, W., Zhang, C., Zhang, C."The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma". International Journal of Oncology 44, no. 6 (2014): 2103-2110. https://doi.org/10.3892/ijo.2014.2356
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