1. Spatial PD‐L1, immune‐cell microenvironment, and genomic copy‐number alteration patterns and drivers of invasive‐disease transition in prospective oral precancer cohort
- Author
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William, William N, Zhang, Jianjun, Zhao, Xin, Parra, Edwin R, Uraoka, Naohiro, Lin, Heather Y, Peng, S Andrew, El‐Naggar, Adel K, Rodriguez‐Canales, Jaime, Song, Jaejoon, Gillenwater, Ann M, Wistuba, Ignacio I, Myers, Jeffrey N, Gold, Kathryn A, Ferrarotto, Renata, Hwu, Patrick, Davoli, Teresa, Lee, J Jack, Heymach, John V, Papadimitrakopoulou, Vassiliki A, and Lippman, Scott M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Dental/Oral and Craniofacial Disease ,Cancer ,Rare Diseases ,Clinical Research ,Humans ,B7-H1 Antigen ,Biomarkers ,Tumor ,Genomics ,Head and Neck Neoplasms ,Lymphocytes ,Tumor-Infiltrating ,Mouth Neoplasms ,Neoplasm Recurrence ,Local ,Prospective Studies ,Squamous Cell Carcinoma of Head and Neck ,Tumor Microenvironment ,copy-number alterations ,genomics ,head and neck cancer ,HPV ,immune profiling ,PD-L1 ,precancer ,T-cells ,tumor microenvironment ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Public health - Abstract
BackgroundStudies of the immune landscape led to breakthrough trials of programmed death-1 (PD-1) inhibitors for recurrent/metastatic head and neck squamous cell carcinoma therapy. This study investigated the timing, influence of somatic copy-number alterations (SCNAs), and clinical implications of PD-L1 and immune-cell patterns in oral precancer (OPC).MethodsThe authors evaluated spatial CD3, CD3/8, and CD68 density (cells/mm2 ) and PD-L1 (membranous expression in cytokeratin-positive intraepithelial neoplastic cells and CD68) patterns by multiplex immunofluorescence in a 188-patient prospective OPC cohort, characterized by clinical, histologic, and SCNA risk factors and protocol-specified primary end point of invasive cancer. The authors used Wilcoxon rank-sum and Fisher exact tests, linear mixed effect models, mediation, and Cox regression and recursive-partitioning analyses.ResultsEpithelial, but not CD68 immune-cell, PD-L1 expression was detected in 28% of OPCs, correlated with immune-cell infiltration, 9p21.3 loss of heterozygosity (LOH), and inferior oral cancer-free survival (OCFS), notably in OPCs with low CD3/8 cell density, dysplasia, and/or 9p21.3 LOH. High CD3/8 cell density in dysplastic lesions predicted better OCFS and eliminated the excess risk associated with prior oral cancer and dysplasia. PD-L1 and CD3/8 patterns revealed inferior OCFS in PD-L1 high intrinsic induction and dysplastic immune-cold subgroups.ConclusionThis report provides spatial insight into the immune landscape and drivers of OPCs, and a publicly available immunogenomic data set for future precancer interrogation. The data suggest that 9p21.3 LOH triggers an immune-hot inflammatory phenotype; whereas increased 9p deletion size encompassing CD274 at 9p24.1 may contribute to CD3/8 and PD-L1 depletion during invasive transition. The inferior OCFS in PD-L1-high, immune-cold OPCs support the development of T-cell recruitment strategies.
- Published
- 2023