The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classic differentiation in pT2-pT4 urothelial bladder cancer.

Background: The basic diagnostic tool of urothelial bladder cancer is the histopathological assessment. However, it is insufficient to accurately predict progression of this disease. There is a need to look for new prognostic factors that will make the therapeutic process more effective. The aim of this study is to evaluate the effect of activation of an PD1 – PD-L1 immune checkpoint in immune effector cells (IECs) and tumor cells, on the development of malignancy in the form of non-classic differentiation in pT2-pT4 urothelial bladder cancer.Materials and methods: 106 patients with stage pT2-pT4 urothelial bladder cancer who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Tumor advancement (pT stage), grade (G) as well as non-classic differentiation frequency and number were evaluated pathologically. In each case the area of the tumor containing PD-L1+ IECs was analyzed. The distribution of PD-L1+ IECs within the tumor was also assessed as dispersed or aggregated. Results: The frequency of non-classic differentiation was significantly higher in urothelial bladder cancer tumors with a dispersed pattern of distribution of PD-L1+ IECs. A correlation between the extent of PD-L1 expression in tumor cells and the non-classic differentiation number in pT2-pT4 stage UBC was identified. Conclusions: The distribution of cells expressing the immune checkpoint biomarker PD-L1 constitutes a new prognostic factor and may play a key role in the selection of individualized immunotherapy. In addition, the evaluation of non-classic differentiation in the tumor may complement the assessment of PD-L1 expression due to its capacity to characterize the current malignant potential of the tumor, whereas the assessment of extent and distribution of PD-L1+ in tumor-associated immune cells indicates the functional status of the immune system.