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免疫检查点蛋白PD-L1和TIM3在小鼠和人类头颈部鳞状细胞癌中的表达

The expression of immune checkpoint proteins PD-L1 and TIM3 in mouse and human head and neck squamous cell carcinoma.

作者信息

Elmusrati Areeg, Wang Cun-Yu

机构信息

Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California, USA.

Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.

出版信息

Eur J Oral Sci. 2024 Oct;132(5):e13010. doi: 10.1111/eos.13010. Epub 2024 Aug 1.

Abstract

The aim of this study was to examine the expression of programmed death-ligand 1 (PD-L1) and of T cell immunoglobulin and mucin domain-containing protein (TIM3) in oral epithelial dysplasia and head and neck squamous cell carcinoma (HNSCC). Mouse HNSCC was induced with 4-nitroquinoline-1 oxide (4NQO). Oral epithelial dysplastic lesions, carcinoma in situ and HNSCC lesions were stained with anti-PD-L1 and TIM3 antibodies. The expression of PD-L1 and TIM3 in tumor cells and immune cells was semiquantitatively measured and compared. In parallel, human dysplasia and HNSCC were stained with anti-PD-L1 and anti-TIM3. The expression pattern of PD-L1 and TIM3 cells was further compared. In human and mouse samples both PD-L1 and TIM3 were found to be expressed in neoplastic and immune cells in HNSCC, but not in dysplasia. There was no significant difference in PD-L1 and TIM3 expression between metastatic and nonmetastatic HNSCC. We conclude that the 4NQO-induced mouse HNSCC model may be an excellent preclinical model for immune checkpoint therapy.

摘要

本研究旨在检测程序性死亡配体1(PD-L1)和T细胞免疫球蛋白黏蛋白结构域蛋白(TIM3)在口腔上皮发育异常及头颈部鳞状细胞癌(HNSCC)中的表达情况。用4-硝基喹啉-1-氧化物(4NQO)诱导小鼠发生HNSCC。采用抗PD-L1和TIM3抗体对口腔上皮发育异常病变、原位癌及HNSCC病变进行染色。对肿瘤细胞和免疫细胞中PD-L1和TIM3的表达进行半定量检测并比较。同时,用抗PD-L1和抗TIM3对人发育异常组织和HNSCC进行染色。进一步比较PD-L1和TIM3细胞的表达模式。在人和小鼠样本中,均发现HNSCC的肿瘤细胞和免疫细胞中表达PD-L1和TIM3,但发育异常组织中未表达。转移性和非转移性HNSCC之间的PD-L1和TIM3表达无显著差异。我们得出结论,4NQO诱导的小鼠HNSCC模型可能是免疫检查点治疗的优秀临床前模型。

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The Evolving Landscape of PD-1/PD-L1 Pathway in Head and Neck Cancer.头颈部肿瘤中 PD-1/PD-L1 通路的演变格局。
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