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Oncogene. 2019 Jun;38(23):4452-4466. doi: 10.1038/s41388-019-0733-6. Epub 2019 Feb 12.

Base excision repair regulates PD-L1 expression in cancer cells.

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Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
Department of Radiotherapy, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia.
Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02114, USA.
International Open Laboratory, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma, 371-8511, Japan.
Education and Research Support Center, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.


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 (H2O2) 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 H2O2. 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.


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