%0 Journal Article
%A Conroy, Jeffrey M
%A Pabla, Sarabjot
%A Nesline, Mary K
%A Glenn, Sean T
%A Papanicolau-Sengos, Antonios
%A Burgher, Blake
%A Andreas, Jonathan
%A Giamo, Vincent
%A Wang, Yirong
%A Lenzo, Felicia L
%A Bshara, Wiam
%A Khalil, Maya
%A Dy, Grace K
%A Madden, Katherine G
%A Shirai, Keisuke
%A Dragnev, Konstantin
%A Tafe, Laura J
%A Zhu, Jason
%A Labriola, Matthew
%A Marin, Daniele
%A McCall, Shannon J
%A Clarke, Jeffrey
%A George, Daniel J
%A Zhang, Tian
%A Zibelman, Matthew
%A Ghatalia, Pooja
%A Araujo-Fernandez, Isabel
%A de la Cruz-Merino, Luis
%A Singavi, Arun
%A George, Ben
%A MacKinnon, Alexander C
%A Thompson, Jonathan
%A Singh, Rajbir
%A Jacob, Robin
%A Kasuganti, Deepa
%A Shah, Neel
%A Day, Roger
%A Galluzzi, Lorenzo
%A Gardner, Mark
%A Morrison, Carl
%T Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors.
%D 2019
%U http://hdl.handle.net/10668/13457
%X PD-L1 immunohistochemistry (IHC) has been traditionally used for predicting clinical responses to immune checkpoint inhibitors (ICIs). However, there are at least 4 different assays and antibodies used for PD-L1 IHC, each developed with a different ICI. We set to test if next generation RNA sequencing (RNA-seq) is a robust method to determine PD-L1 mRNA expression levels and furthermore, efficacy of predicting response to ICIs as compared to routinely used, standardized IHC procedures. A total of 209 cancer patients treated on-label by FDA-approved ICIs, with evaluable responses were assessed for PD-L1 expression by RNA-seq and IHC, based on tumor proportion score (TPS) and immune cell staining (ICS). A subset of serially diluted cases was evaluated for RNA-seq assay performance across a broad range of PD-L1 expression levels. Assessment of PD-L1 mRNA levels by RNA-seq demonstrated robust linearity across high and low expression ranges. PD-L1 mRNA levels assessed by RNA-seq and IHC (TPS and ICS) were highly correlated (p  Measurement of PD-L1 mRNA expression by RNA-seq is comparable to PD-L1 expression by IHC both analytically and clinically in predicting ICI response. RNA-seq has the added advantages of being amenable to standardization and avoidance of interpretation bias. PD-L1 by RNA-seq needs to be validated in future prospective ICI clinical studies across multiple histologies.
%K Atezolizumab
%K Avelumab
%K Biomarker
%K Durvalumab
%K Nivolumab
%K PD-L1
%K Pembrolizumab
%K cancer immunotherapy
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