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Αλέξανδρος Γ. Σφακιανάκης

Wednesday, September 15, 2021

Emerging role of PD-L1 modification in cancer immunotherapy

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Am J Cancer Res. 2021 Aug 15;11(8):3832-3840. eCollection 2021.

ABSTRACT

Accumulating evidence demonstrates that the expression levels of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are regulated at the various levels, including transcription, post-transcriptional modification and post-translational modifications (PTMs). The PTMs of PD-1/PD-L1 contain phosphorylation, ubiquitination, methylation, glycosylation and palmitoylation. Recently, PD-L1 was reported to be acetylated at Lys263 site by p300 and was deacetylated by histone deacetylase 2 (HDAC2). Acetylation of PD-L1 prevented its translocation to the nucleus and led to a reduction of the nuclear portion of PD-L1, resulting in evading immune surveillance of tumor cells. In this review article, we briefly describe the PTMs of PD-1/PD-L1 and mainly summarize the novel findings of PD-L1 acetylation in tumor cells. Moreover, we discuss the associations of PD-L1 acetylation and ubiquitination, phosphorylation and methylation. Furthermore, we highlight that targeting acetylation of PD-L1 by HDAC inhibitors might be useful for enhancing tumor immunotherapy.

PMID:34522452 | PMC:PMC8414388

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