Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors
| Autor: | Lorenzo Galluzzi, Sean T. Glenn, Vincent Giamo, Alexander C. Mackinnon, Jeffrey M. Conroy, Sarabjot Pabla, Jeffrey M. Clarke, Matthew Labriola, Maya Khalil, Isabel Araujo-Fernandez, Carl Morrison, Jonathan Andreas, Rajbir Singh, Blake Burgher, Roger Day, Daniel J. George, Yirong Wang, Laura J. Tafe, Katherine G. Madden, Jason Zhu, Keisuke Shirai, Konstantin H. Dragnev, Mary Nesline, Neel Shah, Robin Jacob, Matthew Zibelman, Felicia L. Lenzo, Shannon J. McCall, Luis de la Cruz-Merino, Arun K Singavi, Antonios Papanicolau-Sengos, Daniele Marin, Pooja Ghatalia, Grace K. Dy, Ben George, Deepa Kasuganti, Wiam Bshara, Tian Zhang, Mark Gardner, Jonathan Thompson |
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| Přispěvatelé: | OmniSeq |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research Cancer immunotherapy B7-H1 Antigen Avelumab 0302 clinical medicine Antineoplastic Agents Immunological Neoplasms Immunology and Allergy Medicine RNA-Seq Atezolizumab biology Melanoma lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunohistochemistry Nivolumab 030220 oncology & carcinogenesis Molecular Medicine Biomarker (medicine) Pembrolizumab medicine.drug Research Article PD-L1 medicine.medical_specialty Immunology lcsh:RC254-282 03 medical and health sciences Internal medicine Humans RNA Messenger Pharmacology cancer immunotherapy business.industry Cancer Biomarker medicine.disease Confidence interval 030104 developmental biology biology.protein Durvalumab business Biomarkers |
| Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-11 (2019) Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | [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 [Conclusions] 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. This research was funded by OmniSeq, Inc. (Buffalo, NY). |
| Databáze: | OpenAIRE |
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