RT Journal Article
T1 Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors.
A1 Conroy, Jeffrey M
A1 Pabla, Sarabjot
A1 Nesline, Mary K
A1 Glenn, Sean T
A1 Papanicolau-Sengos, Antonios
A1 Burgher, Blake
A1 Andreas, Jonathan
A1 Giamo, Vincent
A1 Wang, Yirong
A1 Lenzo, Felicia L
A1 Bshara, Wiam
A1 Khalil, Maya
A1 Dy, Grace K
A1 Madden, Katherine G
A1 Shirai, Keisuke
A1 Dragnev, Konstantin
A1 Tafe, Laura J
A1 Zhu, Jason
A1 Labriola, Matthew
A1 Marin, Daniele
A1 McCall, Shannon J
A1 Clarke, Jeffrey
A1 George, Daniel J
A1 Zhang, Tian
A1 Zibelman, Matthew
A1 Ghatalia, Pooja
A1 Araujo-Fernandez, Isabel
A1 de la Cruz-Merino, Luis
A1 Singavi, Arun
A1 George, Ben
A1 MacKinnon, Alexander C
A1 Thompson, Jonathan
A1 Singh, Rajbir
A1 Jacob, Robin
A1 Kasuganti, Deepa
A1 Shah, Neel
A1 Day, Roger
A1 Galluzzi, Lorenzo
A1 Gardner, Mark
A1 Morrison, Carl
K1 Atezolizumab
K1 Avelumab
K1 Biomarker
K1 Durvalumab
K1 Nivolumab
K1 PD-L1
K1 Pembrolizumab
K1 cancer immunotherapy
AB 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.
YR 2019
FD 2019-01-24
LK http://hdl.handle.net/10668/13457
UL http://hdl.handle.net/10668/13457
LA en
DS RISalud
RD Apr 6, 2025