Open Access

Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer

  • Authors:
    • Zhi‑Hua Liu
    • Fu‑Fu Zheng
    • Yu‑Ling Mao
    • Lie‑Fu Ye
    • Jun Bian
    • De‑Hui Lai
    • Yun‑Lin Ye
    • Yu‑Ping Dai
  • View Affiliations

  • Published online on: April 24, 2017     https://doi.org/10.3892/ol.2017.6080
  • Pages: 4818-4824
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effect of the negative costimulatory molecule programmed death-ligand 1 (PD-L1) on immunotherapy with OK-432, following transurethral resection of bladder tumors in non‑muscle invasive bladder cancer (NMIBC), and to elucidate the underlying mechanism. PD‑L1 was detected by immunohistochemical staining in tumor specimens from 55 cases of NMIBC following postoperative immunotherapy with OK‑432. The PD‑L1 mRNA and protein expression levels were measured in the bladder cancer T24 cell line and the human uroepithelial SV‑HUC‑1 cell line, following treatment with interleukin (IL)‑2, interferon (IFN)‑α and IFN‑γ, by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, respectively. PD‑L1 was widely expressed in the NMIBC tumors, with 56.4% (31/55) of specimens exhibiting positive staining. When compared with PD‑L1‑negative patients, PD-L1-positive patients exhibited significantly increased recurrence [48.4% (15/31) vs. 16.7% (4/24)] and progression [16.1% (5/31) vs. 4.2% (1/24)] rates (P<0.05). RT‑qPCR and western blotting demonstrated that cytokines IL‑2, IFN‑α and IFN-γ markedly upregulated PD‑L1 mRNA expression rates and protein levels in bladder cancer T24 cells (P<0.05), but had no significant effect in non‑tumor SV‑HUC‑1 cells. In conclusion, PD‑L1 expression was negatively‑associated with the efficacy of OK‑432 intravesical immunotherapy in patients with NMIBC. The results indicated that the involved mechanism occurred via upregulation of PD‑L1 by immune cytokines, which in turn suppressed the antitumor effectiveness of the immune system, thereby promoting tumor recurrence and progression.
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June-2017
Volume 13 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liu ZH, Zheng FF, Mao YL, Ye LF, Bian J, Lai DH, Ye YL and Dai YP: Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer. Oncol Lett 13: 4818-4824, 2017
APA
Liu, Z., Zheng, F., Mao, Y., Ye, L., Bian, J., Lai, D. ... Dai, Y. (2017). Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer. Oncology Letters, 13, 4818-4824. https://doi.org/10.3892/ol.2017.6080
MLA
Liu, Z., Zheng, F., Mao, Y., Ye, L., Bian, J., Lai, D., Ye, Y., Dai, Y."Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer". Oncology Letters 13.6 (2017): 4818-4824.
Chicago
Liu, Z., Zheng, F., Mao, Y., Ye, L., Bian, J., Lai, D., Ye, Y., Dai, Y."Effects of programmed death-ligand 1 expression on OK-432 immunotherapy following transurethral resection in non-muscle invasive bladder cancer". Oncology Letters 13, no. 6 (2017): 4818-4824. https://doi.org/10.3892/ol.2017.6080