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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
- Source :
- Cancer. 129:714-727
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- 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).The authors evaluated spatial CD3, CD3/8, and CD68 density (cells/mmEpithelial, 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.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.
- Subjects :
- Cancer Research
Oncology
Subjects
Details
- ISSN :
- 10970142 and 0008543X
- Volume :
- 129
- Database :
- OpenAIRE
- Journal :
- Cancer
- Accession number :
- edsair.doi.dedup.....a76430949630ce38768c9b442fcf082d