Spatial Pd-L1, Immune-Cell Microenvironment, and Genomic Copy-Number Alteration Patterns and Drivers of Invasive-Disease Transition in Prospective Oral Precancer Cohort

Authors

William N William
Jianjun Zhang
Xin Zhao
Edwin R Parra
Naohiro Uraoka
Heather Y Lin
S Andrew Peng
Adel K El-Naggar
Jaime Rodriguez-Canales
Jaejoon Song
Ann M Gillenwater
Ignacio I Wistuba
Jeffrey N Myers
Kathryn A Gold
Renata Ferrarotto
Patrick Hwu
Teresa Davoli
J Jack Lee
John V Heymach
Vassiliki A Papadimitrakopoulou
Scott M Lippman

Publication Date

3-1-2023

Journal

Cancer

Abstract

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/mm

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.

Keywords

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

Comments

Supplementary Material

PMID: 36597662

DOI

10.1002/cncr.34607

PMID

36597662

PMCID

PMC10508302

PubMedCentral® Posted Date

September 2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes