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胶质母细胞瘤患者外周免疫系统的调节与治疗及肿瘤进展相关——来自IMMO-GLIO-01试验的病例报告

Modulations in the Peripheral Immune System of Glioblastoma Patient Is Connected to Therapy and Tumor Progression-A Case Report from the IMMO-GLIO-01 Trial.

作者信息

Rühle Paul F, Goerig Nicole, Wunderlich Roland, Fietkau Rainer, Gaipl Udo S, Strnad Annedore, Frey Benjamin

机构信息

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Research Unit of Radiation Cytogenetics, Helmholtz Center Munich, Neuherberg, Germany.

出版信息

Front Neurol. 2017 Jun 23;8:296. doi: 10.3389/fneur.2017.00296. eCollection 2017.

Abstract

Immune responses are important for efficient tumor elimination, also in immune privileged organs such as the brain. Fostering antitumor immunity has therefore become an important challenge in cancer therapy. This cannot only be achieved by immunotherapies as already standard treatments such as radiotherapy and chemotherapy modify the immune system. Consequently, the understanding of how the tumor, the tumor microenvironment, and immune system are modulated by cancer therapy is required for prognosis, prediction, and therapy adaption. The prospective, explorative, and observational IMMO-GLIO-01 trial was initiated to examine the detailed immune status and its modulation of about 50 patients suffering from primary glioblastoma multiforme (GBM) or anaplastic astrocytoma during standard therapy. Prior to the study, a flow cytometry-based assay was established allowing the analysis of 34 immune cell subsets and their activation state. Here, we present the case of the first and longest accompanied patient, a 53-year-old woman suffering from GBM in the front left lobe. In context of tumor progression and therapy, we describe the modulation of the peripheral immune status over 17 months. Distinct immune modulations that were connected to therapy response or tumor progression were identified. , a shift of CD4:CD8 ratio was observed that correlated with tumor progression. Twice we observed a unique composition of peripheral immune cells that correlated with tumor progression. Thus, following up these immune modulations in a closely-meshed manner is of high prognostic and predictive relevance for supporting personalized therapy and increasing therapy success. : ClinicalTrials.gov, identifier NCT02022384 (registered retrospectively on 13th of December, 2013).

摘要

免疫反应对于有效消除肿瘤至关重要,在诸如大脑等免疫豁免器官中亦是如此。因此,增强抗肿瘤免疫力已成为癌症治疗中的一项重要挑战。这不仅可以通过免疫疗法来实现,因为诸如放疗和化疗等已有的标准治疗方法也会改变免疫系统。因此,了解癌症治疗如何调节肿瘤、肿瘤微环境和免疫系统对于预后、预测和治疗调整是必要的。前瞻性、探索性和观察性的IMMO-GLIO-01试验启动,以检查约50例原发性多形性胶质母细胞瘤(GBM)或间变性星形细胞瘤患者在标准治疗期间的详细免疫状态及其调节情况。在该研究之前,建立了一种基于流式细胞术的检测方法,可分析34种免疫细胞亚群及其激活状态。在此,我们介绍首例且随访时间最长的患者,一名53岁患有左额叶GBM的女性。在肿瘤进展和治疗的背景下,我们描述了17个月外周免疫状态的调节情况。识别出了与治疗反应或肿瘤进展相关的不同免疫调节。观察到CD4:CD8比值的变化与肿瘤进展相关。我们两次观察到外周免疫细胞的独特组成与肿瘤进展相关。因此,紧密跟踪这些免疫调节对于支持个性化治疗和提高治疗成功率具有高度的预后和预测相关性。:ClinicalTrials.gov,标识符NCT02022384(于2013年12月13日追溯注册)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cfd/5481307/206339731c96/fneur-08-00296-g001.jpg

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