| Title: |
Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma |
| Authors: |
Yu H.; Chen Z.; Ballman K. V.; Watson M. A.; Govindan R.; Lanc I.; Beer D. G.; Bueno R.; Chirieac L. R.; Chui M. H.; Chen G.; Franklin W. A.; Gandara D. R.; Genova C.; Brovsky K. A.; Joshi M. -B. M.; Merrick D. T.; Richards W. G.; Rivard C. J.; Harpole D. H.; Tsao M. -S.; van Bokhoven A.; Shepherd F. A.; Hirsch F. R. |
| Contributors: |
Yu, H.; Chen, Z.; Ballman, K. V.; Watson, M. A.; Govindan, R.; Lanc, I.; Beer, D. G.; Bueno, R.; Chirieac, L. R.; Chui, M. H.; Chen, G.; Franklin, W. A.; Gandara, D. R.; Genova, C.; Brovsky, K. A.; Joshi, M. -B. M.; Merrick, D. T.; Richards, W. G.; Rivard, C. J.; Harpole, D. H.; Tsao, M. -S.; van Bokhoven, A.; Shepherd, F. A.; Hirsch, F. R. |
| Publisher Information: |
Elsevier Inc; 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA |
| Publication Year: |
2019 |
| Collection: |
Università degli Studi di Genova: CINECA IRIS |
| Subject Terms: |
Early-stage squamous cell lung cancer; Immune gene signature; PD-L1 expression; Prognosi; Tumor mutation burden; Aged; B7-H1 Antigen; Carcinoma; Squamous Cell; Female; Human; Interferon-gamma; Lung Neoplasm; Male; Mutation; Neoplasm Staging; Tumor Burden |
| Description: |
Objectives: Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC. Methods: A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens. Results: The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/30253973; info:eu-repo/semantics/altIdentifier/wos/WOS:000454018600016; volume:14; firstpage:25; lastpage:36; numberofpages:12; journal:JOURNAL OF THORACIC ONCOLOGY; https://hdl.handle.net/11567/1028981 |
| DOI: |
10.1016/j.jtho.2018.09.006 |
| Availability: |
https://hdl.handle.net/11567/1028981; https://doi.org/10.1016/j.jtho.2018.09.006 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.FB13821F |
| Database: |
BASE |