自噬
免疫抑制
癌症研究
程序性细胞死亡
癌细胞
封锁
PD-L1
癌症
下调和上调
免疫检查点
巴非霉素
生物
细胞生物学
免疫系统
化学
免疫学
细胞凋亡
免疫疗法
受体
生物化学
基因
遗传学
作者
Te‐Fu Tsai,An‐Chen Chang,Po‐Chun Chen,Chao‐Yen Ho,Hung‐En Chen,Kan‐Sen Chou,Thomas I‐Sheng Hwang
摘要
A high basal level of autophagic flux in bladder cancer (BC) cells prevents cell death and weakens chemotherapy efficacy. However, how autophagy influences cancer-associated immunosuppression in BC remains undetermined. In this study, we observed a negative correlation between the autophagy-related markers LC3-II and programmed death ligand-1 (PD-L1) in BC cells. The autophagy inhibitors chloroquine (CQ) and bafilomycin A1 (Baf-A1) increased PD-L1 expression in BC cells through the ERK-JNK-c-Jun signal-transduction pathway. Moreover, the treatment of BC cells with CQ and Baf-A1 inhibited hsa-microRNA-34a (miR-34a) expression and miR-34a overexpression in BC cells prevented the autophagy blockade-induced PD-L1 expression; a negative correlation between miR-34a and PD-L1 expression was observed during treatment with autophagy inhibitors. Furthermore, miR-34a overexpression induced the cytotoxic activity of natural killer cells against BC cells. Our results provide evidence that autophagy blockade and its regulatory pathway affect cancer-associated immunosuppression through PD-L1 elevation. Thus, the coadministration of autophagy inhibitors and a PD-L1 immune checkpoint blockade provides a potential therapeutic approach for treating BC.
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