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Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma

  • Authors:
    • Weijie Zhong
    • Xin Xu
    • Zhigang Zhu
    • Li Yang
    • Hong Du
    • Zhongjun Xia
    • Zhaohu Yuan
    • Huabao Xiong
    • Qinghua Du
    • Yaming Wei
    • Qingshan Li
  • View Affiliations / Copyright

    Affiliations: The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Geriatrics, Hematology and Oncology Ward, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Department of Pathology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Department of Hematological Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China, Department of Blood Transfusion, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029-5674, USA
    Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1528-1538
    |
    Published online on: March 5, 2018
       https://doi.org/10.3892/ijo.2018.4299
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Abstract

Rituximab resistance has become increasingly common in patients with diffuse large B cell lymphoma (DLBCL). However, the mechanisms involved remain unclear. In this study, we aimed to examine the effect of rituximab on interleukin (IL)-17A and to investigate the role of IL-17A in rituximab resistance and its prognostic value in patients with DLBCL. Our retrospective analysis revealed that rituximab increased IL-6 expression levels in patients with DLBCL, and the increased IL-6 levels in turn induced the differentiation of Th17 and IL-17+Foxp3+ Treg cells, which secreted IL-17A both in vivo and in vitro. We then examined the effects of IL-17A on the apoptosis and proliferation of, and p53 expression in DLBCL cells, and found that IL-17A prevented rituximab-induced apoptosis and promoted the proliferation of DLBCL cells by suppressing p53 expression in vitro. The survival data of 73 patients with DLBCL suggested that high peripheral blood levels of IL-17A predicted an unfavorable survival. On the whole, our data indicate that rituximab promotes Th17 and IL-17+Foxp3+ Treg cells to secrete IL-17A, which in turn promotes rituximab resistance, partially by suppressing p53 expression and inhibiting rituximab-induced DLBCL cell apoptosis. IL-17A may thus prove to be a useful prognostic marker in patients with DLBCL.
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Copy and paste a formatted citation
Spandidos Publications style
Zhong W, Xu X, Zhu Z, Yang L, Du H, Xia Z, Yuan Z, Xiong H, Du Q, Wei Y, Wei Y, et al: Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma. Int J Oncol 52: 1528-1538, 2018.
APA
Zhong, W., Xu, X., Zhu, Z., Yang, L., Du, H., Xia, Z. ... Li, Q. (2018). Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma. International Journal of Oncology, 52, 1528-1538. https://doi.org/10.3892/ijo.2018.4299
MLA
Zhong, W., Xu, X., Zhu, Z., Yang, L., Du, H., Xia, Z., Yuan, Z., Xiong, H., Du, Q., Wei, Y., Li, Q."Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma". International Journal of Oncology 52.5 (2018): 1528-1538.
Chicago
Zhong, W., Xu, X., Zhu, Z., Yang, L., Du, H., Xia, Z., Yuan, Z., Xiong, H., Du, Q., Wei, Y., Li, Q."Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma". International Journal of Oncology 52, no. 5 (2018): 1528-1538. https://doi.org/10.3892/ijo.2018.4299
Copy and paste a formatted citation
x
Spandidos Publications style
Zhong W, Xu X, Zhu Z, Yang L, Du H, Xia Z, Yuan Z, Xiong H, Du Q, Wei Y, Wei Y, et al: Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma. Int J Oncol 52: 1528-1538, 2018.
APA
Zhong, W., Xu, X., Zhu, Z., Yang, L., Du, H., Xia, Z. ... Li, Q. (2018). Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma. International Journal of Oncology, 52, 1528-1538. https://doi.org/10.3892/ijo.2018.4299
MLA
Zhong, W., Xu, X., Zhu, Z., Yang, L., Du, H., Xia, Z., Yuan, Z., Xiong, H., Du, Q., Wei, Y., Li, Q."Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma". International Journal of Oncology 52.5 (2018): 1528-1538.
Chicago
Zhong, W., Xu, X., Zhu, Z., Yang, L., Du, H., Xia, Z., Yuan, Z., Xiong, H., Du, Q., Wei, Y., Li, Q."Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma". International Journal of Oncology 52, no. 5 (2018): 1528-1538. https://doi.org/10.3892/ijo.2018.4299
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