原发性口腔鳞状细胞癌免疫微环境中Gasdermin-E介导的免疫功能变化

IF 4 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral oncology Pub Date : 2024-11-04 DOI:10.1016/j.oraloncology.2024.107088
Xiangjun Wang , Xingyu Chen , Zi Mei
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引用次数: 0

摘要

在原发性口腔鳞状细胞癌(OSCC)中,肿瘤微环境(TME)是一个由细胞和细胞元素组成的高度复杂的生态系统。肿瘤免疫微环境(TIME)的特点是存在大量免疫细胞,而肿瘤内的细胞毒性淋巴细胞(CTL)却很少。因此,如何招募更多的细胞毒性淋巴细胞浸润肿瘤核心已成为一项紧迫的科学挑战。Gasdermin E (GSDME)作为热蛋白沉积过程中的关键效应蛋白,在抗肿瘤治疗中发挥着重要作用。本文利用化学诱变剂4-硝基喹啉N-氧化物(4-NQO)分别诱导Gsdme基因敲除(KO)小鼠和同一品系的野生型(WT)小鼠发生原发性OSCC。通过对两种小鼠的免疫功能进行比较分析,我们发现了一些耐人寻味的现象:GSDME的存在有助于增加淋巴细胞向肿瘤部位的浸润,从而有效地改善TIME。我们的研究结果阐明,GSDME的缺失会促进原发性OSCC的发展,并伴随着恶性程度的显著增加。此外,我们的数据还描述了GSDME的存在与宿主机体免疫反应性之间的正向相互关系,而宿主机体免疫反应性会延长原发性OSCC的发病时间。
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Changes of immune function mediated by Gasdermin-E in the immune microenvironment of primary oral squamous cell carcinoma
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.
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来源期刊
Oral oncology
Oral oncology 医学-牙科与口腔外科
CiteScore
8.70
自引率
10.40%
发文量
505
审稿时长
20 days
期刊介绍: Oral Oncology is an international interdisciplinary journal which publishes high quality original research, clinical trials and review articles, editorials, and commentaries relating to the etiopathogenesis, epidemiology, prevention, clinical features, diagnosis, treatment and management of patients with neoplasms in the head and neck. Oral Oncology is of interest to head and neck surgeons, radiation and medical oncologists, maxillo-facial surgeons, oto-rhino-laryngologists, plastic surgeons, pathologists, scientists, oral medical specialists, special care dentists, dental care professionals, general dental practitioners, public health physicians, palliative care physicians, nurses, radiologists, radiographers, dieticians, occupational therapists, speech and language therapists, nutritionists, clinical and health psychologists and counselors, professionals in end of life care, as well as others interested in these fields.
期刊最新文献
Editorial Board Efficacy of boron neutron capture therapy (BNCT) for patients with oral cancer Evaluation of a comprehensive set of normal tissue complication probability models for patients with head and neck cancer in an international cohort Microscopic findings in oral squamous cell carcinoma with cystic spaces and clear cells mimicking mucoepidermoid carcinoma: A detailed case report Letter to the editor, “Mitoxantrone hydrochloride liposome injection for the treatment of Recurrent/Metastatic head and neck squamous cell carcinoma: A multicenter, open-label, single-arm, phase 1b study.”
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