Novel pdl1 regulation mechanism provides opportunity for prostate cancer treatment

Access through your institution Buy or subscribe A new study in _Oncogene_ describes an epigenetic mechanism of PDL1 regulation by cancer cells and a therapeutic approach to enhance efficacy

of PDL1 blockade in prostate cancer. The researchers showed that the histone acetyltransferases p300 and CBP were recruited to the promoter of _CD274_ (encoding PDL1) by transcription

factor IRF1, which resulted in acetylation of histone H3 at the _CD274_ promoter and subsequent _CD274_ transcription. The p300/CBP inhibitor A485 blocked transcription of _CD274_ and

stopped exosomal PDL1 secretion. Upregulation of PDL1 expression is a resistance mechanism to antibody-based PDL1 blockade in prostate cancer. Cutting off PDL1 secretion at transcription by

inhibiting p300/CBP combined with anti-PDL1 antibodies demonstrated increased efficacy in a syngeneic mouse model of prostate cancer (TRAMP-C2). This is a preview of subscription content,

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institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * Liu, J. et al. p300/CBP inhibition enhances the efficacy of programmed death-ligand 1

blockade treatment in prostate cancer. _Oncogene_ https://doi.org/10.1038/s41388-020-1270-z (2020) Article  PubMed  PubMed Central  Google Scholar  Download references AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Nature Reviews Urology http://www.nature.com/nrurol/ Tim Thomas Authors * Tim Thomas View author publications You can also search for this author inPubMed Google

Scholar CORRESPONDING AUTHOR Correspondence to Tim Thomas. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Thomas, T. Novel PDL1 regulation mechanism

provides opportunity for prostate cancer treatment. _Nat Rev Urol_ 17, 256 (2020). https://doi.org/10.1038/s41585-020-0323-y Download citation * Published: 20 April 2020 * Issue Date: May

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