口腔鳞状细胞癌恶性转化的免疫肿瘤学特征。

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

机构信息

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.

Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.

出版信息

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.

DOI:10.1016/j.oooo.2023.07.009

PMID:37739913

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.

摘要

目的

本研究旨在确定口腔鳞状细胞癌（OSCC）手术切缘（TM）中的免疫肿瘤学（IO）特征，该特征涉及恶性转化过程。

研究设计

在机构审查委员会批准下，使用免疫组织化学法对 73 例 OSCC 的 TM 进行程序性死亡配体 1（PD-L1）免疫生物标志物检测。对 5 对 TM 和侵袭性肿瘤（T）进行了 NanoString 770 IO 焦点基因集分析。在口腔潜在恶性细胞系（OPMC）中研究了 PD-L1 对干扰素-γ（IFN-γ）的反应调节。

结果

上皮边缘的 PD-L1 表达与其下方免疫细胞的表达直接相关（P =.0082）。差异基因表达显示 TM 相对于 T 对的 PD-L1 和 IFN-γ 6 基因特征下调。TM 中 CD8 和巨噬细胞更高。TM 相对于 T 的 CNTFR、LYZ、C7、RORC 和 FGF13 下调。T 相对于 TM 的 TDO2、ADAM12、MMP1、LAMC2、MB21D1、TYMP、OASL、COL5A1、耗尽的_CD8、Tregs 和 NK_CD56dim 上调。最后，IFN-γ诱导 OPMC 中 PD-L1 的上调。