Immuno-oncologic signature of malignant transformation in oral squamous cell carcinoma

Manar Elnaggar; Risa Chaisuparat; Ioana Ghita; Soren M Bentzen; Donita Dyalram; Robert A Ord; Joshua E Lubek; Rania H Younis

doi:10.1016/j.oooo.2023.07.009

Immuno-oncologic signature of malignant transformation in oral squamous cell carcinoma

Oral Surg Oral Med Oral Pathol Oral Radiol. 2023 Nov;136(5):612-622. doi: 10.1016/j.oooo.2023.07.009. Epub 2023 Jul 13.

Authors

Manar Elnaggar¹, Risa Chaisuparat², Ioana Ghita³, Soren M Bentzen⁴, Donita Dyalram⁵, Robert A Ord⁵, Joshua E Lubek⁵, Rania H Younis⁶

Affiliations

¹ Department of Oncology and Diagnostic Sciences, Division of Oral and Maxillofacial Pathology, University of Maryland School of Dentistry, Baltimore, MD, USA; Department of Oral Pathology, Faculty of Dentistry, Alexandria University, Alexandria, Egypt; Department of Oral Pathology, Faculty of Dentistry, Arab Academy for Science and Technology, El Alamein, Egypt.
² Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
³ Department of Oncology and Diagnostic Sciences, Division of Oral and Maxillofacial Pathology, University of Maryland School of Dentistry, Baltimore, MD, USA.
⁴ Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA; Biostatistics Core, Institute of Clinical and Translational Research, University of Maryland, Baltimore, MD, USA; Biostatistics Division, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
⁵ Department of Oral and Maxillofacial Surgery, University of Maryland School of Dentistry, Baltimore, MD, USA; Head and Neck Surgery Department of Oral and Maxillofacial Surgery, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
⁶ Department of Oncology and Diagnostic Sciences, Division of Oral and Maxillofacial Pathology, University of Maryland School of Dentistry, Baltimore, MD, USA; Department of Oral Pathology, Faculty of Dentistry, Alexandria University, Alexandria, Egypt; Division of Tumor Immunology and Immunotherapy, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, UMB, Maryland, USA; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: Ryounis1@umaryland.edu.

PMID: 37739913
DOI: 10.1016/j.oooo.2023.07.009

Abstract

Objective: The purpose of this study is to identify the immuno-oncologic (IO) signature at the surgical tumor margin (TM) of oral squamous cell carcinoma (OSCC) that is involved in the process of malignant transformation.

Study design: Under institutional review board approval, TM of 73 OSCC were investigated using immunohistochemistry for the immune biomarker, programmed death ligand-1 (PD-L1). NanoString 770 IO-focused gene set was analyzed in 5 pairs of TM and invasive tumor (T). PD-L1 regulation in response to interferon-gamma (IFN-γ) was investigated in an oral potentially malignant cell line (OPMC).

Results: Programmed death ligand-1 expression in the epithelial margin directly correlated with its expression in the underlying immune cells (P = .0082). Differential gene expression showed downregulation of PD-L1 and IFN-γ 6 gene signature in the TM relative to T pair.CD8 and macrophages were higher in TM. CNTFR, LYZ, C7, RORC, and FGF13 downregulation in T relative to TM. TDO2, ADAM12, MMP1, LAMC2, MB21D1, TYMP, OASL, COL5A1, exhausted_CD8, Tregs,and NK_CD56dim were upregulated in T relative to TM. Finally, IFN-γ induced upregulation of PD-L1 in the OPMC.

Conclusions: Our work suggests a role for IFN-γ in PD-L1 upregulation in OPMC and presents novel IO transcriptional signatures for frankly invasive OSCC relative to TM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen / genetics
CD8-Positive T-Lymphocytes
Carcinoma, Squamous Cell* / pathology
Head and Neck Neoplasms*
Humans
Interferon-gamma
Mouth Neoplasms* / pathology
Squamous Cell Carcinoma of Head and Neck

Substances

B7-H1 Antigen
Interferon-gamma