Bitar Lynn, Schumann Ulrike, König Renate, Zipp Frauke, Schmidt Mirko H H
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network, University Medical Center of The Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Institute of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden School of Medicine, 01307 Dresden, Germany.
Cancers (Basel). 2021 Jul 14;13(14):3524. doi: 10.3390/cancers13143524.
Communication signals and signaling pathways are often studied in different physiological systems. However, it has become abundantly clear that the immune system is not self-regulated, but functions in close association with the nervous system. The neural-immune interface is complex; its balance determines cancer progression, as well as autoimmune disorders. Immunotherapy remains a promising approach in the context of glioblastoma multiforme (GBM). The primary obstacle to finding effective therapies is the potent immunosuppression induced by GBM. Anti-inflammatory cytokines, induction of regulatory T cells, and the expression of immune checkpoint molecules are the key mediators for immunosuppression in the tumor microenvironment. Immune checkpoint molecules are ligand-receptor pairs that exert inhibitory or stimulatory effects on immune responses. In the past decade, they have been extensively studied in preclinical and clinical trials in diseases such as cancer or autoimmune diseases in which the immune system has failed to maintain homeostasis. In this review, we will discuss promising immune-modulatory targets that are in the focus of current clinical research in glioblastoma, but are also in the precarious position of potentially becoming starting points for the development of autoimmune diseases like multiple sclerosis.
通信信号和信号通路通常在不同的生理系统中进行研究。然而,已经非常清楚的是,免疫系统并非自我调节,而是与神经系统密切相关地发挥作用。神经-免疫界面很复杂;其平衡决定癌症进展以及自身免疫性疾病。在多形性胶质母细胞瘤(GBM)的背景下,免疫疗法仍然是一种有前景的方法。寻找有效疗法的主要障碍是GBM诱导的强效免疫抑制。抗炎细胞因子、调节性T细胞的诱导以及免疫检查点分子的表达是肿瘤微环境中免疫抑制的关键介质。免疫检查点分子是对免疫反应发挥抑制或刺激作用的配体-受体对。在过去十年中,它们在癌症或自身免疫性疾病等疾病的临床前和临床试验中得到了广泛研究,在这些疾病中免疫系统未能维持体内平衡。在本综述中,我们将讨论有前景的免疫调节靶点,这些靶点是当前胶质母细胞瘤临床研究的重点,但也处于可能成为像多发性硬化症这样的自身免疫性疾病发展起点的不稳定位置。