Study deciphers enigmatic mechanism of pd-l1 overexpression

Access through your institution Buy or subscribe Anticancer immunotherapy targeting the PD-1–PD-L1 axis results in dramatic tumour responses, but in only a small proportion of patients;

thus, biomarkers that reliably identify these patients are needed. Now, a novel genetic mechanism that drives overexpression of PD-L1 has been discovered, with implications for patient

stratification. “To detect PD-L1 SVs, we performed genome-wide mapping of SV-associated breakpoints using whole-genome sequencing data, because this methodology has recently been reported to

successfully identify novel activating SVs, such as those involving _GFI1_ or _TERT_,” Ogawa explains. PD-L1 SVs were identified in 13 of 49 (26.5%) ATL samples. In each of the 13 samples,

a PD-L1 transcript with an aberrant 3' untranslated region (UTR) was generated and overexpression of PD-L1 was observed, with evidence indicating that the 3'-UTR alterations

delayed clearance of the transcripts. Importantly, all of the aberrant forms of PD-L1 retained the extracellular domains and could bind to PD-1, suggesting that the mutant forms have the

capacity to activate immunosuppressive signals in T cells. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to

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support REFERENCES * Kataoka, K. _ et al_. Aberrant _PD-L1_ expression through 3'-UTR disruption in multiple cancer. _Nature_ http://dx.doi.org/10.1038/nature18294 (2016) Download

references Authors * David Killock View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Killock, D. Study deciphers enigmatic mechanism of PD-L1 overexpression. _Nat Rev Clin Oncol_ 13, 395 (2016). https://doi.org/10.1038/nrclinonc.2016.97 Download citation *

Published: 07 June 2016 * Issue Date: July 2016 * DOI: https://doi.org/10.1038/nrclinonc.2016.97 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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