Department of Neurological Surgery and Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
The Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC 27710, USA.
Cells. 2021 Aug 9;10(8):2032. doi: 10.3390/cells10082032.
Despite the important evolution of immunotherapeutic agents, brain tumors remain, in general, refractory to immune therapeutics. Recent discoveries have revealed that the glioma microenvironment includes a wide variety of immune cells in various states that play an important role in the process of tumorigenesis. Anti-tumor immune activity may be occurring or induced in immunogenic hot spots or at the invasive edge of central nervous system (CNS) tumors. Understanding the complex heterogeneity of the immune microenvironment in gliomas will likely be the key to unlocking the full potential of immunotherapeutic strategies. An essential consideration will be the induction of immunological effector responses in the setting of the numerous aspects of immunosuppression and evasion. As such, immune therapeutic combinations are a fundamental objective for clinical studies in gliomas. Through immune profiling conducted on immune competent murine models of glioma and ex vivo human glioma tissue, we will discuss how the frequency, distribution of immune cells within the microenvironment, and immune modulatory processes, may be therapeutically modulated to lead to clinical benefits.
尽管免疫治疗药物有了重要的发展,但脑肿瘤通常仍然对免疫治疗有抗性。最近的发现表明,神经胶质瘤微环境中包含各种处于不同状态的免疫细胞,这些细胞在肿瘤发生过程中发挥着重要作用。抗肿瘤免疫活性可能发生在免疫原性热点或中枢神经系统(CNS)肿瘤的浸润边缘。了解神经胶质瘤中免疫微环境的复杂异质性可能是充分发挥免疫治疗策略潜力的关键。一个重要的考虑因素将是在众多免疫抑制和逃避方面诱导免疫效应反应。因此,免疫治疗联合是神经胶质瘤临床研究的一个基本目标。通过对免疫功能正常的神经胶质瘤小鼠模型和体外人神经胶质瘤组织进行免疫分析,我们将讨论如何调节微环境中免疫细胞的频率、分布和免疫调节过程,以带来临床获益。