Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma |
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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 Fred R Hirsch |
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Institution: | 1. Division of Medical Oncology, University of Colorado Denver, Aurora, Colorado;2. Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, New York;3. Washington University School of Medicine, St. Louis, Missouri;4. University of Michigan, Ann Arbor, Michigan;5. Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts;6. Harvard Medical School, Boston, Massachusetts;7. University Health Network/Princess Margaret Cancer Centre and University of Toronto, Toronto, Canada;8. Department of Pathology, University of Colorado Denver, Aurora, Colorado;9. University of California Davis Comprehensive Cancer Center, Sacramento, California;10. Lung Cancer Unit, San Martino Hospital, Genoa, Italy;11. Duke University, Durham, North Carolina |
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Abstract: | ObjectivesAnti–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.MethodsA 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.ResultsThe 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.ConclusionsEvaluation 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. |
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Keywords: | PD-L1 expression Tumor mutation burden Immune gene signature Prognosis Early-stage squamous cell lung cancer |
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