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VEGFC促进对脑肿瘤的免疫监视
2020-01-16 16:57

耶鲁大学医学院Akiko Iwasaki和Jean-Leon Thomas合作研究显示,VEGF-C驱动的淋巴引流可对脑肿瘤进行免疫监视。这一研究成果2020年1月15日在线发表在国际学术期刊《自然》上。

使用胶质母细胞瘤小鼠模型,研究人员发现脑膜淋巴管系统能产生更强的抵抗脑肿瘤的免疫反应。当肿瘤局限在中枢神经系统时,CD8 T细胞介导的免疫反应对胶质母细胞瘤抗原抵抗力非常有限,导致肿瘤不受控制地生长。

然而,异位表达血管内皮生长因子C(VEGF-C)促进颈外侧深淋巴结中CD8 T细胞的启动增强,CD8 T细胞迁移到肿瘤内,快速清除胶质母细胞瘤和维持持久的抗肿瘤记忆反应。

此外,转染表达VEGF-C 的mRNA协同检查点阻断疗法,可以根除现有的胶质母细胞瘤。这些结果揭示了VEGF-C促进肿瘤免疫监视的能力,并提出了治疗脑肿瘤的新方法。

据悉,由于缺乏淋巴引流,免疫系统对中枢神经系统内病原体和肿瘤的监视是有限的。然而,脑膜淋巴网络特征的揭示帮助人们理解先前未知的大脑内表达的抗原如何引起免疫应答。尽管人们对脑膜淋巴系统发育和结构的认知有所增加,但是该网络在大脑保护性抗原特异性免疫反应方面的作用仍不清楚。

附:英文原文

Title: VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours

Author: Eric Song, Tianyang Mao, Huiping Dong, Ligia Simoes Braga Boisserand, Salli Antila, Marcus Bosenberg, Kari Alitalo, Jean-Leon Thomas, Akiko Iwasaki

Issue&Volume: 2020-01-15

Abstract: Immune surveillance against pathogens and tumours in the central nervous system is thought to be limited owing to the lack of lymphatic drainage. However, the characterization of the meningeal lymphatic network has shed light on previously unappreciated ways that an immune response can be elicited to antigens that are expressed in the brain1,2,3. Despite progress in our understanding of the development and structure of the meningeal lymphatic system, the contribution of this network in evoking a protective antigen-specific immune response in the brain remains unclear. Here, using a mouse model of glioblastoma, we show that the meningeal lymphatic vasculature can be manipulated to mount better immune responses against brain tumours. The immunity that is mediated by CD8 T cells to the glioblastoma antigen is very limited when the tumour is confined to the central nervous system, resulting in uncontrolled tumour growth. However, ectopic expression of vascular endothelial growth factor C (VEGF-C) promotes enhanced priming of CD8 T cells in the draining deep cervical lymph nodes, migration of CD8 T cells into the tumour, rapid clearance of the glioblastoma and a long-lasting antitumour memory response. Furthermore, transfection of an mRNA construct that expresses VEGF-C works synergistically with checkpoint blockade therapy to eradicate existing glioblastoma. These results reveal the capacity of VEGF-C to promote immune surveillance of tumours, and suggest a new therapeutic approach to treat brain tumours.

DOI: 10.1038/s41586-019-1912-x

Source: https://www.nature.com/articles/s41586-019-1912-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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