Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma.

Abstract

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 independently prognostic for patient outcomes.

CONCLUSIONS:

Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.

• Authors: Hui Yu, Zhengming Chen, Karla V Ballman, Mark A Watson, Ramaswamy Govindan, Irena Lanc, David G Beer, Raphael Bueno, Lucian R Chirieac, Michael Herman Chui, Guoan Chen, Wilbur A Franklin, David R Gandara, Carlo Genova, Kristine A Brovsky, Mary-Beth M Joshi, Daniel T Merrick, William G Richards, Christopher J Rivard, David H Harpole, Ming-Sound Tsao, Adrie van Bokhoven, Frances A Shepherd, Fred R Hirsch
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 14 Issue 1 Pg. 25-36 (01 2019) ISSN: 1556-1380 [Electronic] United States
• PMID: 30253973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 International Association for the Study of Lung Cancer. All rights reserved.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Interferon-gamma

Topics

• Aged
• B7-H1 Antigen (biosynthesis, genetics, immunology)
• Carcinoma, Squamous Cell (genetics, immunology, pathology)
• Female
• Humans
• Interferon-gamma (genetics, immunology)
• Lung Neoplasms (genetics, immunology, pathology)
• Male
• Mutation
• Neoplasm Staging
• Prognosis
• Tumor Burden