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靶向树突状细胞-T 细胞轴以开发胶质母细胞瘤的有效免疫治疗

英文原题:Targeting the dendritic cell-T cell axis to develop effective immunotherapies for glioblastoma.

PubMed 2023/10/20(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

胶质母细胞瘤是一种侵袭性原发性脑肿瘤,20 多年来治疗进展甚微。

中文摘要

胶质母细胞瘤是一种侵袭性原发性脑肿瘤,过去20多年来治疗进展有限。为应对这一迫切的临床需求,多种免疫治疗策略正在开发,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,但迄今尚未带来显著临床获益。疗效不佳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起的全身免疫系统改变。此外,T细胞是控制肿瘤的关键效应细胞,树突状细胞在T细胞活化中同样发挥重要作用;新近证据提示,胶质母细胞瘤患者的树突状细胞群可能严重受损。本综述介绍目前正在开发的胶质母细胞瘤免疫治疗方法及其面临的挑战,并特别强调树突状细胞-T细胞轴的关键作用。我们提出若干可用于增加树突状细胞数量、增强其功能的策略,并认为将这些策略与靶向T细胞的方法联合,可能实现有效的肿瘤控制。

展开英文摘要原文

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.

论文信息

作者
Gardam B、Gargett T、Brown MP、Ebert LM
单位
Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia.Australia
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2023
原文标识
PubMed 37928547 · DOI 10.3389/fimmu.2023.1261257