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Spatial PD‐L1, immune‐cell microenvironment, and genomic copy‐number alteration patterns and drivers of invasive‐disease transition in prospective oral precancer cohort
- 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;
- Lippman, Scott M
- et al.
Published Web Location
https://doi.org/10.1002/cncr.34607Abstract
Background
Studies 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).Methods
The 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.Results
Epithelial, 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.Conclusion
This 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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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