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胶质瘤中的基因改变重塑肿瘤免疫微环境并影响免疫介导的治疗。

Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies.

作者信息

Garcia-Fabiani Maria B, Haase Santiago, Comba Andrea, Carney Stephen, McClellan Brandon, Banerjee Kaushik, Alghamri Mahmoud S, Syed Faisal, Kadiyala Padma, Nunez Felipe J, Candolfi Marianela, Asad Antonela, Gonzalez Nazareno, Aikins Marisa E, Schwendeman Anna, Moon James J, Lowenstein Pedro R, Castro Maria G

机构信息

Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United States.

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United States.

出版信息

Front Oncol. 2021 Jun 8;11:631037. doi: 10.3389/fonc.2021.631037. eCollection 2021.

Abstract

High grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors. Currently, immunotherapies represent an appealing approach to treat malignant gliomas, as the pre-clinical data has been encouraging. However, the translation of the discoveries from the bench to the bedside has not been as successful as with other types of cancer, and no long-lasting clinical benefits have been observed for glioma patients treated with immune-mediated therapies so far. This review aims to discuss our current knowledge about gliomas, their molecular particularities and the impact on the tumor immune microenvironment. Also, we discuss several murine models used to study these therapies pre-clinically and how the model selection can impact the outcomes of the approaches to be tested. Finally, we present different immunotherapy strategies being employed in clinical trials for glioma and the newest developments intended to harness the immune system against these incurable brain tumors.

摘要

高级别胶质瘤是发生于中枢神经系统的恶性脑肿瘤,可见于各年龄段患者。目前,包括手术及放化疗在内的标准治疗方案的生存率为14至17个月。因此,迫切需要为这些恶性脑肿瘤开发新的治疗策略。目前,免疫疗法是治疗恶性胶质瘤的一种有吸引力的方法,因为临床前数据令人鼓舞。然而,从实验室到临床的转化并不像其他类型癌症那样成功,到目前为止,接受免疫介导疗法治疗的胶质瘤患者尚未观察到持久的临床益处。本综述旨在讨论我们目前对胶质瘤的认识、其分子特性以及对肿瘤免疫微环境的影响。此外,我们还讨论了几种用于临床前研究这些疗法的小鼠模型,以及模型选择如何影响待测试方法的结果。最后,我们介绍了目前在胶质瘤临床试验中采用的不同免疫治疗策略,以及旨在利用免疫系统对抗这些无法治愈的脑肿瘤的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab89/8217836/c749c7ccf13c/fonc-11-631037-g001.jpg

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