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Gasdermin-E 介导的免疫功能变化在原发性口腔鳞状细胞癌免疫微环境中的作用。

Changes of immune function mediated by Gasdermin-E in the immune microenvironment of primary oral squamous cell carcinoma.

机构信息

Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, Henan Province 450000, China.

Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.

出版信息

Oral Oncol. 2024 Dec;159:107088. doi: 10.1016/j.oraloncology.2024.107088. Epub 2024 Nov 4.

DOI:10.1016/j.oraloncology.2024.107088
PMID:39500059
Abstract

In primary oral squamous cell carcinoma (OSCC), the tumor microenvironment (TME) constitutes a highly intricate ecosystem comprised of cellular and acellular elements. The tumor immune microenvironment (TIME) is characterized by the presence of a broad of immune cells, while there is a scarcity of cytotoxic lymphocytes (CTLs) intratumorally. Consequently, the recruitment of a larger cohort of CTLs to infiltrate the tumor core has emerged as a pressing scientific challenge. Gasdermin E (GSDME), as a pivotal effector protein in pyroptosis, plays a significant role in anti-tumor therapy. Here, primary OSCC was induced by Gsdme knockout (KO) mice and wild type (WT) mice of the same strain respectively, using the chemical mutagen 4-Nitroquinoline N-oxide (4-NQO). Through comparative analysis of immune function between the two kinds of mice, intriguing observations have been elucidated, the presence of GSDME was instrumental in augmenting the infiltration of lymphocytes towards the neoplastic site, effectively ameliorating the TIME. Our findings elucidated that the absence of GSDME promotes the development of primary OSCC, accompanied by a notable increase in malignancy. Furthermore, our data delineated a positive inter-relationship between the presence of GSDME and the host organism's immunological reactivity, which enhances the TIME in primary OSCC.

摘要

在原发性口腔鳞状细胞癌(OSCC)中,肿瘤微环境(TME)构成了一个由细胞和无细胞成分组成的高度复杂的生态系统。肿瘤免疫微环境(TIME)的特征是存在广泛的免疫细胞,而肿瘤内的细胞毒性淋巴细胞(CTL)却很少。因此,招募更多的 CTL 浸润肿瘤核心已成为一个紧迫的科学挑战。Gasdermin E(GSDME)作为细胞焦亡的关键效应蛋白,在抗肿瘤治疗中发挥重要作用。在这里,我们分别使用化学诱变剂 4-硝基喹啉 N-氧化物(4-NQO)诱导 Gsdme 敲除(KO)小鼠和同系野生型(WT)小鼠发生原发性 OSCC。通过对两种小鼠免疫功能的比较分析,我们揭示了一些有趣的观察结果,即 GSDME 的存在有助于增加淋巴细胞向肿瘤部位的浸润,有效改善 TIME。我们的研究结果表明,GSDME 的缺失促进了原发性 OSCC 的发展,并伴随着恶性程度的显著增加。此外,我们的数据还描绘了 GSDME 的存在与宿主免疫反应之间的正相关关系,这增强了原发性 OSCC 的 TIME。

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