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肿瘤源性基质金属蛋白酶-9有助于肿瘤耐受。

Cancer-derived matrix metalloproteinase-9 contributes to tumor tolerance.

机构信息

Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.

出版信息

J Cancer Res Clin Oncol. 2011 Oct;137(10):1525-33. doi: 10.1007/s00432-011-1010-4. Epub 2011 Aug 11.

Abstract

BACKGROUND AND AIMS

Tumor-specific T regulatory cells (Treg) play a critical role in tumor cell survival. The development of tumor-specific Treg is not fully understood. This study aims to elucidate the role of matrix metalloproteinase (MMP)9 in tumor tolerance development.

METHODS

We recruited 38 patients with laryngeal cancer (LC) in this study. MMP9 levels in the LC were measured by western blotting. Immune cells were isolated from LC tissue for indicated experiments. The cells' activities were characterized by flow cytometry.

RESULTS

High levels of MMP9 were detected in LC that plays a critical role in the development of tolerogenic dendritic cells and LC-specific Tregs. The isolated LC Tregs have the ability to suppress tumor-specific CD8 T cells in a tumor antigen-specific manner.

CONCLUSIONS

This study reveals a novel mechanism in tumor tolerance in which MMP9 plays a critical role in tumor survival. The data imply that MMP9 may be a potential target in the treatment of malignant tumors.

摘要

背景与目的

肿瘤特异性调节性 T 细胞(Treg)在肿瘤细胞存活中发挥着关键作用。肿瘤特异性 Treg 的发展尚未完全阐明。本研究旨在阐明基质金属蛋白酶(MMP)9 在肿瘤耐受发展中的作用。

方法

本研究纳入了 38 例喉癌(LC)患者。通过 Western blot 检测 LC 中的 MMP9 水平。从 LC 组织中分离免疫细胞进行相关实验。通过流式细胞术鉴定细胞活性。

结果

高表达的 MMP9 在 LC 中被检测到,在诱导耐受树突状细胞和 LC 特异性 Treg 的发展中发挥着关键作用。分离的 LC Treg 具有以肿瘤抗原特异性方式抑制肿瘤特异性 CD8 T 细胞的能力。

结论

本研究揭示了肿瘤耐受中的一种新机制,其中 MMP9 在肿瘤存活中发挥着关键作用。数据表明 MMP9 可能是恶性肿瘤治疗的潜在靶点。

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