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The prognostic significance of PD-L1 in bladder cancer

  • Authors:
    • Yide Huang
    • Shu-Dong Zhang
    • Cian McCrudden
    • Kwok-Wah Chan
    • Yao Lin
    • Hang-Fai Kwok

  • View Affiliations

  • Published online on: April 27, 2015     https://doi.org/10.3892/or.2015.3933
  • Pages: 3075-3084
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Abstract

Immunotherapy is a promising strategy for the treatment of various types of cancer. An antibody that targets programmed death ligand-1 (PD-L1) pathway has been shown to be active towards various types of cancer, including melanoma and lung cancer. MPDL3280A, an anti‑PD-L1 antibody, has shown clear clinical activity in PD-L1-overexpressing bladder cancer with an objective response rate of 40-50%, resulting in a breakthrough therapy designation granted by FDA. These events pronounce the importance of targeting the PD-L1 pathway in the treatment of bladder cancer. In the present study, we investigated the prognostic significance of the expression of three genes in the PD-L1 pathway, including PD-L1, B7.1 and PD-1, in three independent bladder cancer datasets in the Gene Expression Omnibus database. PD-L1, B7.1 and PD-1 were significantly associated with clinicopathological parameters indicative of a more aggressive phenotype of bladder cancer, such as a more advanced stage and a higher tumor grade. In addition, a high level expression of PD-L1 was associated with reduced patient survival. Of note, the combination of PD-L1 and B7.1 expression, but not other combinations of the three genes, were also able to predict patient survival. Our findings support the development of anti-PD-L1, which blocks PD-L1-PD-1 and B7.1-PD-L1 interactions, in treatment of bladder cancer. The observations were consistent in the three independent bladder cancer datasets consisting of a total of 695 human bladder specimens. The datasets were then assessed and it was found that the expression levels of the chemokine CC-motif ligand (CCL), CCL3, CCL8 and CCL18, were correlated with the PD-L1 expression level, while ADAMTS13 was differentially expressed in patients with a different survival status (alive or deceased). Additional investigations are required to elucidate the role of these genes in the PD-L1-mediated immune system suppression and bladder cancer progression. In conclusion, findings of this study suggested that PD-L1 is an important prognostic marker and a therapeutic target for bladder cancer.
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June-2015
Volume 33 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Huang Y, Zhang S, McCrudden C, Chan K, Lin Y and Kwok H: The prognostic significance of PD-L1 in bladder cancer. Oncol Rep 33: 3075-3084, 2015
APA
Huang, Y., Zhang, S., McCrudden, C., Chan, K., Lin, Y., & Kwok, H. (2015). The prognostic significance of PD-L1 in bladder cancer. Oncology Reports, 33, 3075-3084. https://doi.org/10.3892/or.2015.3933
MLA
Huang, Y., Zhang, S., McCrudden, C., Chan, K., Lin, Y., Kwok, H."The prognostic significance of PD-L1 in bladder cancer". Oncology Reports 33.6 (2015): 3075-3084.
Chicago
Huang, Y., Zhang, S., McCrudden, C., Chan, K., Lin, Y., Kwok, H."The prognostic significance of PD-L1 in bladder cancer". Oncology Reports 33, no. 6 (2015): 3075-3084. https://doi.org/10.3892/or.2015.3933