Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.
Translational Oncology Laboratory, Centre for Cancer Biology, University of South Australia and South Australia (SA) Pathology, Adelaide, SA, Australia.
Front Immunol. 2023 Oct 20;14:1261257. doi: 10.3389/fimmu.2023.1261257. eCollection 2023.
Glioblastoma is an aggressive primary brain tumor that has seen few advances in treatments for over 20 years. In response to this desperate clinical need, multiple immunotherapy strategies are under development, including CAR-T cells, immune checkpoint inhibitors, oncolytic viruses and dendritic cell vaccines, although these approaches are yet to yield significant clinical benefit. Potential reasons for the lack of success so far include the immunosuppressive tumor microenvironment, the blood-brain barrier, and systemic changes to the immune system driven by both the tumor and its treatment. Furthermore, while T cells are essential effector cells for tumor control, dendritic cells play an equally important role in T cell activation, and emerging evidence suggests the dendritic cell compartment may be deeply compromised in glioblastoma patients. In this review, we describe the immunotherapy approaches currently under development for glioblastoma and the challenges faced, with a particular emphasis on the critical role of the dendritic cell-T cell axis. We suggest a number of strategies that could be used to boost dendritic cell number and function and propose that the use of these in combination with T cell-targeting strategies could lead to successful tumor control.
胶质母细胞瘤是一种侵袭性原发性脑肿瘤,20 多年来治疗方法鲜有进展。针对这一迫切的临床需求,目前正在开发多种免疫疗法策略,包括 CAR-T 细胞、免疫检查点抑制剂、溶瘤病毒和树突状细胞疫苗,尽管这些方法尚未带来显著的临床获益。迄今为止缺乏成功的潜在原因包括免疫抑制性肿瘤微环境、血脑屏障以及肿瘤及其治疗引发的全身性免疫系统变化。此外,尽管 T 细胞是控制肿瘤的重要效应细胞,但树突状细胞在 T 细胞激活中也起着同样重要的作用,新出现的证据表明,树突状细胞在胶质母细胞瘤患者中可能受到严重损害。在这篇综述中,我们描述了目前正在开发用于治疗胶质母细胞瘤的免疫疗法方法以及面临的挑战,特别强调了树突状细胞-T 细胞轴的关键作用。我们提出了一些可以用来增加树突状细胞数量和功能的策略,并提出将这些策略与 T 细胞靶向策略结合使用可能会导致成功的肿瘤控制。
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