MP027: Up-regulation of programmed death-l-ligand 1 (PD-L1) expression as an immune escape mechanismin in the cisplatin-treated human bladder cancer cells
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  • 2017-12-25,
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細胞程式死亡-配體1 (PD-L1)之正調控表現可作為膀胱癌細胞順鉑處理後之
免疫逃脫機制
黃一勝1,3,4、林致凡2、林宜佳1,4、蔡德甫1,4、陳宏恩1、仇光宇1,4
1新光醫院泌尿科、2新光醫院中央研究室、3台北醫學大學醫學院、4輔仁大學醫學院
Up-regulation of programmed death-l-ligand 1 (PD-L1) expression as an immune escape mechanismin in the cisplatin-treated human bladder cancer cells
Thomas I-Sheng Hwang1,3,4, Ji-Fan Lin2, Yi-Chia Lin1,4, Te-Fu Tsai 1,4, Hung-En Chen1 and Kuang-Yu Chou1,4
Department of Urology1, Central Laboratory2, Shin Kong Wu Ho-Su Memorial Hospital;Division of Urology, School of Medicine, Fu-Jen Catholic University3; Department of Urology, Taipei Medical University4, Taipei, Taiwan.
 
Abstract
Background: The current standard for muscle-invasive bladder cancer (BC) patients is cisplatin-based neoadjuvant chemotherapy. However, the prognosis of the cancer patients has not been substantially improved and several different mechanisms could be involved. Previously, we showed that BC cells promote autophagy as a resistant mechanism upon cisplatin treatment. Cancer immunoresistance and immune escape are major obstacle in chemotherapy. However, the effects of cisplatin on the immune responses of BC cells are note clear. In the present studies, we investigate the expression of immunoresistance molecular PD-L1 on cisplatin-treated 5637 and T24 cells.
Methods: Human immortalized urothelial (SV-Huc-1) and bladder cancer (5637 and T24) cell lines were used in this study. The expression of PD-L1 mRNA and protein in control or cisplatin-treated cells were detected by quantitative RT-PCR and Western blot. PD-L1 knockdown in cisplatin treated cells was conducted using lenti-viral based shRNA. Cell viability in cisplatin-treated cells with or without PD-L1 knockdown was monitored by tetrazolium salt WST-1. Cell signaling pathways, including AKT, ERK, MAPK and JNK, were detected by Western blot. PD98059 and Baf A1 were used as inhibitors for MAPK and autophagy, respectively.
Results: Up-regulation of PD-L1 expression was detected in 5637 and T24 cells treated with various concentrations of cisplatin.Increased levels of ERK, AKT, and JNK phosphorylation were observed in cisplatin-treated human BC cells, butonly pretreatment of PD98059 in cisplatin-treated cells attenuated the expression of PD-L1, suggesting that cisplatin-induced PD-L1 expression in BC cells is dependent of ERK pathway. In addition, inhibitionof autophagy using Baf A1 did not suppressed cisplatin-induced PD-L1, indicating cisplatin not only induces the intrinsic protective autophagy but up-regulates immune checkpoint, PD-L1, as an immune escape pro-survival mechanism in human bladder cancer cells.
Conclusions: Cisplatin induces PD-L1 in human BC cells, suggesting an immune escape mechanism other than intrinsic protective autophagy. Targeting ERK pathway could be considered as therapeutic options in cisplatin resistant.
Keywords:  Autophagy, immune checkpoint, PD-L1, Bladder cancer cells.
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    發表時間 :
    2017-12-25 14:13:51
    觀看數 :
    304
    發表人 :
    TUA秘書處
    部門 :
    台灣泌尿科醫學會
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