胶质瘤的免疫抑制。
Immune suppression in gliomas.
机构信息
Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, 303 Research Drive, 220 Sands Bldg, Durham, NC, 27710, USA.
出版信息
J Neurooncol. 2021 Jan;151(1):3-12. doi: 10.1007/s11060-020-03483-y. Epub 2020 Jun 15.
INTRODUCTION
The overall survival in patients with gliomas has not significantly increased in the modern era, despite advances such as immunotherapy. This is in part due to their notorious ability to suppress local and systemic immune responses, severely restricting treatment efficacy.
METHODS
We have reviewed the preclinical and clinical evidence for immunosuppression seen throughout the disease process in gliomas. This review aims to discuss the various ways that brain tumors, and gliomas in particular, co-opt the body's immune system to evade detection and ensure tumor survival and proliferation.
RESULTS
A multitude of mechanisms are discussed by which neoplastic cells evade detection and destruction by the immune system. These include tumor-induced T-cell and NK cell dysfunction, regulatory T-cell and myeloid-derived suppressor cell expansion, M2 phenotypic transformation in glioma-associated macrophages/microglia, upregulation of immunosuppressive glioma cell surface factors and cytokines, tumor microenvironment hypoxia, and iatrogenic sequelae of immunosuppressive treatments.
CONCLUSIONS
Gliomas create a profoundly immunosuppressive environment, both locally within the tumor and systemically. Future research should aim to address these immunosuppressive mechanisms in the effort to generate treatment options with meaningful survival benefits for this patient population.
简介
尽管免疫疗法等方面取得了进展,但胶质瘤患者的总体生存率在现代并未显著提高。部分原因是其抑制局部和全身免疫反应的能力非常强,从而严重限制了治疗效果。
方法
我们回顾了胶质瘤在疾病过程中各个阶段出现的免疫抑制的临床前和临床证据。本综述旨在讨论多种方式,即脑肿瘤,尤其是神经胶质瘤,如何利用机体的免疫系统来逃避检测并确保肿瘤的存活和增殖。
结果
讨论了多种肿瘤细胞逃避免疫系统检测和破坏的机制。这些机制包括肿瘤诱导的 T 细胞和 NK 细胞功能障碍、调节性 T 细胞和髓源性抑制细胞的扩增、与胶质瘤相关的巨噬细胞/小胶质细胞中 M2 表型的转化、免疫抑制性胶质瘤细胞表面因子和细胞因子的上调、肿瘤微环境缺氧以及免疫抑制治疗的医源性后果。
结论
胶质瘤在肿瘤内部和全身形成了一种高度免疫抑制的环境。未来的研究应致力于解决这些免疫抑制机制,为这一患者群体提供具有显著生存获益的治疗选择。