Base excision repair regulates PD-L1 expression in cancer cells

Tiara Bunga Mayang Permata, Yoshihiko Hagiwara, Hiro Sato, Takaaki Yasuhara, Takahiro Oike, Soehartati Argadikoesoema, Kathryn D. Held, Takashi Nakano, Atsushi Shibata

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Programmed death-ligand 1 (PD-L1) is a key factor influencing cancer immunotherapy; however, the regulation of PD-L1 expression in cancer cells remains unclear, particularly regarding DNA damage, repair and its signalling. Herein, we demonstrate that oxidative DNA damage induced by exogenously applied hydrogen peroxide (H 2 O 2 ) upregulates PD-L1 expression in cancer cells. Further, depletion of the base excision repair (BER) enzyme DNA glycosylase augments PD-L1 upregulation in response to H 2 O 2 . PD-L1 upregulation in BER-depleted cells requires ATR/Chk1 kinase activities, demonstrating that PD-L1 upregulation is mediated by DNA damage signalling. Further analysis of The Cancer Genome Atlas revealed that the expression of PD-L1 is negatively correlated with that of the BER/single-strand break repair (SSBR) and tumours with low BER/SSBR gene expression show high microsatellite instability and neoantigen production. Hence, these results suggest that PD-L1 expression is regulated in cancer cells via the DNA damage signalling and neoantigen–interferon-γ pathway under oxidative stress.

Original languageEnglish
JournalOncogene
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Dive into the research topics of 'Base excision repair regulates PD-L1 expression in cancer cells'. Together they form a unique fingerprint.

Cite this