研究动态
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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.

发表日期:2023 Jul 13
作者: Manar Elnaggar, Risa Chaisuparat, Ioana Ghita, Soren M Bentzen, Donita Dyalram, Robert A Ord, Joshua E Lubek, Rania H Younis
来源: Cell Death & Disease

摘要:

本研究的目的是确定参与恶性转化过程的口腔鳞状细胞癌(OSCC)手术肿瘤边缘(TM)处的免疫肿瘤学(IO)特征。经过机构审查委员会批准,使用免疫组化技术研究了73例OSCC的TM,通过研究免疫生物标志物程序性死亡配体-1(PD-L1)。在5对TM和浸润性肿瘤(T)中分析了NanoString 770种IO相关基因组。研究了口腔潜在恶性细胞系(OPMC)中PD-L1对干扰素-γ(IFN-γ)的调节。上皮边缘中的程序性死亡配体-1表达与底层免疫细胞的表达直接相关(P = 0.0082)。差异基因表达显示,在TM与T成对样本中,PD-L1和IFN-γ 6种基因签名被下调。TM中CD8和巨噬细胞含量较高。T与TM相比,T中CNTFR、LYZ、C7、RORC和FGF13表达下调。T相对于TM中,TDO2、ADAM12、MMP1、LAMC2、MB21D1、TYMP、OASL、COL5A1、exhausted_CD8、Tregs和NK_CD56dim表达上调。最后,IFN-γ导致OPMC中PD-L1的上调。我们的工作表明IFN-γ在OPMC中上调PD-L1的作用,并提出了与TM相比的明显侵袭性OSCC的新型IO转录标志。版权所有 © 2023 Elsevier公司。保留所有权利。
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.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).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.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.Copyright © 2023 Elsevier Inc. All rights reserved.