DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells

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DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells

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Title: DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells
Author: Sato, Hiro; Niimi, Atsuko; Yasuhara, Takaaki; Permata, Tiara Bunga Mayang; Hagiwara, Yoshihiko; Isono, Mayu; Nuryadi, Endang; Sekine, Ryota; Oike, Takahiro; Kakoti, Sangeeta; Yoshimoto, Yuya; Held, Kathryn D.; Suzuki, Yoshiyuki; Kono, Koji; Miyagawa, Kiyoshi; Nakano, Takashi; Shibata, Atsushi

Note: Order does not necessarily reflect citation order of authors.

Citation: Sato, H., A. Niimi, T. Yasuhara, T. B. M. Permata, Y. Hagiwara, M. Isono, E. Nuryadi, et al. 2017. “DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells.” Nature Communications 8 (1): 1751. doi:10.1038/s41467-017-01883-9. http://dx.doi.org/10.1038/s41467-017-01883-9.
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Abstract: Accumulating evidence suggests that exogenous cellular stress induces PD-L1 upregulation in cancer. A DNA double-strand break (DSB) is the most critical type of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has not been investigated. Here we show that PD-L1 expression in cancer cells is upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD-L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1 activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation. Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and provide mechanistic insight into how PD-L1 expression is regulated after DSBs.
Published Version: doi:10.1038/s41467-017-01883-9
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701012/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493034
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