Mangani Davide, Weller Michael, Roth Patrick
Laboratory of Molecular Neuro-Oncology, Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.
Laboratory of Molecular Neuro-Oncology, Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland; Center for Neuroscience, University of Zurich, Zurich, Switzerland.
Biochem Pharmacol. 2017 Apr 15;130:1-9. doi: 10.1016/j.bcp.2016.12.011. Epub 2016 Dec 22.
Glioblastoma remains a fatal tumor despite increased knowledge regarding the complex signalling pathways that drive this devastating disease. Recently, immunotherapeutic approaches have shown remarkable and durable responses in various cancers including metastatic melanoma and advanced non-small cell lung cancer. So far, it remains unclear whether these immunotherapeutics may also work against glioblastoma and other tumors residing in the central nervous system. It is well known that patients with glioblastoma suffer from profound local immunosuppression that represents the major hurdle to overcome in the context of immunotherapy. Several studies have demonstrated that this immunosuppressive phenotype is orchestrated by glioma-derived membrane-bound and soluble factors as well as the particular microenvironment within the brain. Here, we discuss the molecular and cellular pathways involved in glioblastoma-mediated inhibition of the immune system and highlight possible treatment approaches aiming at reinvigorating anti-tumor immune responses.
尽管人们对驱动这种毁灭性疾病的复杂信号通路的了解有所增加，但胶质母细胞瘤仍然是一种致命肿瘤。最近，免疫治疗方法在包括转移性黑色素瘤和晚期非小细胞肺癌在内的各种癌症中显示出显著且持久的反应。到目前为止，尚不清楚这些免疫疗法是否也能对抗胶质母细胞瘤和其他位于中枢神经系统的肿瘤。众所周知，胶质母细胞瘤患者存在严重的局部免疫抑制，这是免疫治疗背景下需要克服的主要障碍。多项研究表明，这种免疫抑制表型是由胶质瘤衍生的膜结合和可溶性因子以及脑内特定的微环境所调控的。在此，我们讨论胶质母细胞瘤介导的免疫系统抑制所涉及的分子和细胞途径，并强调旨在重振抗肿瘤免疫反应的可能治疗方法。
