title: The prognostic significance of PD-L1 in bladder cancer.
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.
authors.affiliation: College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, P.R. China.
authors.forename: Yide
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Cancer Research and Cell Biology and School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Shu-Dong
authors.initials: SD
authors.lastname: Zhang
authors.affiliation: Center for Cancer Research and Cell Biology and School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Cian
authors.initials: C
authors.lastname: McCrudden
authors.affiliation: Department of Pathology, University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
authors.affiliation: College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, P.R. China.
authors.forename: Hang-Fai
authors.initials: HF
authors.lastname: Kwok
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C000594389:atezolizumab