Autophagy blockade potentiates cancer-associated immunosuppression through programmed death ligand-1 upregulation in bladder cancer

Te Fu Tsai, An Chen Chang, Po Chun Chen, Chao Yen Ho, Hung En Chen, Kuang Yu Chou, Thomas I.Sheng Hwang

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3587-3597
Number of pages11
JournalJournal of Cellular Physiology
Volume237
Issue number9
DOIs
Publication statusPublished - Sept 2022
Externally publishedYes

Keywords

  • autophagy
  • bladder cancer
  • Hsa-miR-34a
  • immunosuppression
  • PD-L1

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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