Acetylation increases expression, interaction with TRAPPC4 and surface localization of PD-L1
In: Discover Oncology, Jg. 14 (2023), Heft 1, S. 1-14
Online
academicJournal
Zugriff:
Abstract PD-L1 is an immune checkpoint inhibitor, whose surface expression may be exploited by cancer cells to escape T cell-mediated immune recognition. PD-L1 expression and nuclear localization can be affected by epigenetic modifications, such as acetylation. In this study, we showed that VPA, a class I/IIa HDAC inhibitor, upregulated PD-L1 expression on the surface of pancreatic cancer cells. To this effect contributed the increased transcription, in correlation with histone acetylation of the PD-L1 gene and the acetylation of PD-L1 protein, which led to an increased interaction with TRAPPC4, molecule involved in PD-L1 recycling to the cell membrane. Interestingly, the BRD4 inhibitor JQ-1, counteracted PD-L1 transcription and reduced its surface expression, suggesting that such a combination could improve the outcome of VPA treatment, also because it increased the cytotoxic effect of VPA. Also considering that this HDACi did not upregulate PD-L2 and that the supernatant of VPA-treated cancer cells did not increase PD-L1 expression on the surface of macrophages exposed to it.
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Acetylation increases expression, interaction with TRAPPC4 and surface localization of PD-L1
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Autor/in / Beteiligte Person: | Maria Anele Romeo ; Maria Saveria Gilardini Montani ; Santarelli, Roberta ; Benedetti, Rossella ; Arena, Andrea ; Cirone, Mara |
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Zeitschrift: | Discover Oncology, Jg. 14 (2023), Heft 1, S. 1-14 |
Veröffentlichung: | Springer, 2023 |
Medientyp: | academicJournal |
ISSN: | 2730-6011 (print) |
DOI: | 10.1007/s12672-023-00766-4 |
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