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

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.

Calcium Channel Blocker Nifedipine Suppresses Colorectal Cancer Progression and Immune Escape by Preventing NFAT2 Nuclear Translocation

“…Programmed death-ligand 1 (PD-L1), also known as surface antigen differentiation cluster 274 (CD274) or B7 homolog (B7-H1), is a type 1 transmembrane protein encoded by the CD274 gene. Upregulation of PD-L1 expression can enable cancer cells to escape host immune recognition, thereby increasing the risk of tumor invasion and metastasis (Francisco et al, 2010;Goltz et al, 2016;Liu et al, 2017;Yaghoubi et al, 2019;Zhou et al, 2017).…”

<p>Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis</p>

“…The characteristics of the included studies are shown in Table 1. The 27 studies included 4,032 patients; 716,18,20,21,23,24,26studies originated from Asian countries/regions (Japan, Taiwan, China), 925,27,29-35studies were multicentre and global studies, and the remaining studies originated from the United States, Germany, and France. The sample size ranged from 37 to 423.…”

Patient-Derived Non-Muscular Invasive Bladder Cancer Xenografts of Main Molecular Subtypes of the Tumor for Anti-Pd-l1 Treatment Assessment

“…Programmed death-ligand 1 (PD-L1) is a member of the B7 family of costimulatory molecules; it is a cell surface glycoprotein that promotes apoptosis by binding to its surface receptor, programmed cell death-1 (PD-1), in T cells and B cells, thereby inhibiting host immune function. PD-L1 has also been implicated in tumor immune escape [3,4,5].…”