Extracellular Vesicles of Salivary Adenoid Cystic Carcinoma Suppress Immune Microenvironment in Lung.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral diseases Pub Date : 2025-08-16 DOI:10.1111/odi.70065

Yue Lou, Longping Liu, Yuping Liu, Zheng Zhou, Lijing Zhu, Yajuan Cui, Huaxiu Sun, Xuan Zhou, Chuanxiang Zhou, Tiejun Li

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引用次数: 0

Abstract

Objective: Salivary adenoid cystic carcinoma (SACC) frequently metastasizes to the lung and affects patient survival. Extracellular vesicles (EVs) have significant effects in the tumor pre-metastatic niche (PMN). In this study, we aimed to investigate immune changes in the lung pre-metastatic microenvironment of SACC.

Methods: A pre-metastatic microenvironment was established using SACC-derived EVs at different time points. Labeled EVs were injected into mice to examine their different organ distributions. Flow cytometry was conducted to analyze the immune cell populations. In vitro, the same amount of SACC-derived EVs or EV-depleted conditional medium was added to macrophages to stimulate polarization.

Results: The SACC-derived EVs colonized mostly in the lung and were engulfed by lung interstitial macrophages (IM). At different time points, the SACC-derived EVs induced decreased total macrophage, natural killer cell, and T cell populations, especially CD8⁺ T cells. They also increased the M2 macrophage composition and regulatory T cell population. The in vitro study showed that SACC-derived EVs induce a mixed M1/M2 phenotype, but this effect was eliminated with the EV-depleted media.

Conclusions: SACC-derived EVs circulate to the lung, where they are engulfed by IM and induce an immunosuppressive environment. In vitro experiments revealed that cargos on EVs could mediate macrophage polarization.

查看原文本刊更多论文

涎腺样囊性癌细胞外囊泡抑制肺免疫微环境。

目的：涎腺样囊性癌（SACC）常转移至肺部，影响患者生存。细胞外囊泡（EVs）在肿瘤转移前生态位（PMN）中具有重要作用。在这项研究中，我们旨在研究SACC肺转移前微环境的免疫变化。方法：利用sacc衍生的ev在不同时间点建立转移前微环境。将标记的ev注射到小鼠体内，观察其不同的器官分布。流式细胞术分析免疫细胞群。在体外，向巨噬细胞中加入等量的sacc衍生的ev或ev耗尽的条件培养基来刺激极化。结果：sacc衍生的ev主要定植于肺，并被肺间质巨噬细胞（IM）吞噬。在不同的时间点，sacc衍生的ev诱导巨噬细胞、自然杀伤细胞和T细胞总数减少，尤其是CD8+ T细胞。它们还增加了M2巨噬细胞的组成和调节性T细胞的数量。体外研究表明，sacc衍生的ev诱导了混合的M1/M2表型，但这种影响在ev耗尽的培养基中被消除。结论：sacc衍生的ev循环到肺部，在那里它们被IM吞噬并诱导免疫抑制环境。体外实验表明，电动汽车上的货物可介导巨噬细胞极化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.