학술논문
Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors
Document Type
article
Author
Jeffrey M. Conroy; Sarabjot Pabla; Mary K. Nesline; Sean T. Glenn; Antonios Papanicolau-Sengos; Blake Burgher; Jonathan Andreas; Vincent Giamo; Yirong Wang; Felicia L. Lenzo; Wiam Bshara; Maya Khalil; Grace K. Dy; Katherine G. Madden; Keisuke Shirai; Konstantin Dragnev; Laura J. Tafe; Jason Zhu; Matthew Labriola; Daniele Marin; Shannon J. McCall; Jeffrey Clarke; Daniel J. George; Tian Zhang; Matthew Zibelman; Pooja Ghatalia; Isabel Araujo-Fernandez; Luis de la Cruz-Merino; Arun Singavi; Ben George; Alexander C. MacKinnon; Jonathan Thompson; Rajbir Singh; Robin Jacob; Deepa Kasuganti; Neel Shah; Roger Day; Lorenzo Galluzzi; Mark Gardner; Carl Morrison
Source
Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-11 (2019)
Subject
Language
English
ISSN
2051-1426
Abstract
Abstract Background 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. Methods 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. Results 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