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胶质瘤的免疫逃逸机制。

Mechanisms of immune evasion by gliomas.

机构信息

Department of Surgery, The University of Chicago Pritzker School of Medicine, Chicago, IL, USA.

出版信息

Adv Exp Med Biol. 2012;746:53-76. doi: 10.1007/978-1-4614-3146-6_5.

Abstract

A major contributing factor to glioma development and progression is its ability to evade the immune system. This chapter will explore the mechanisms utilized by glioma to mediate immunosuppression and immune evasion. These include intrinsic mechanisms linked to its location within the brain and interactions between glioma cells and immune cells. Lack of recruitment of naïve effector immune cells perhaps accounts for most of the immune suppression mediated by these tumor cells. This is enhanced by increased recruitment of microglia which resemble immature antigen presenting cells that are unable to support T-cell mediated immunity. Furthermore, secreted factors like TGF-β, COX-2 and IL-10, altered costimulatory molecules and inhibition of STAT-3 all contribute to the recruitment and expansion of regulatory T cells, which further modulate the immunosuppressive environment of glioma. In light of these findings, multiple immunotherapeutic treatment modalities are currently being explored.

摘要

导致神经胶质瘤发生和进展的一个主要因素是其逃避免疫系统的能力。本章将探讨神经胶质瘤介导免疫抑制和免疫逃逸的机制。这些机制包括与其在大脑中的位置相关的内在机制以及神经胶质瘤细胞与免疫细胞之间的相互作用。幼稚效应免疫细胞的募集不足可能是这些肿瘤细胞介导的免疫抑制的大部分原因。这种情况因小胶质细胞的募集增加而加剧,小胶质细胞类似于不能支持 T 细胞介导免疫的未成熟抗原呈递细胞。此外,转化生长因子-β (TGF-β)、环氧化酶-2 (COX-2) 和白细胞介素-10 (IL-10) 等分泌因子、改变的共刺激分子以及 STAT-3 的抑制作用都有助于调节性 T 细胞的募集和扩增,从而进一步调节神经胶质瘤的免疫抑制环境。鉴于这些发现,目前正在探索多种免疫治疗治疗方法。

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