CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Human gamma-delta (γδ) T cell therapy for glioblastoma: A novel alternative to overcome challenges of adoptive immune cell therapy.
然而,γδ T细胞作为人外周血中T细胞的一小部分(1-5%),与常规αβ T细胞相比,相对未知。
胶质母细胞瘤是最常见的脑恶性肿瘤,预后极差。许多使用各种靶向治疗药物的临床试验均以失败告终,近期使用检查点抑制剂的临床试验也未能为胶质母细胞瘤患者提供生存获益。过继性 T 细胞转移被认为是一种新型治疗方法,在初步临床研究中显示出前景。然而,临床结果并不一致,当前用于胶质母细胞瘤治疗的过继性 T 细胞转移策略存在若干局限性。作为一种替代性细胞疗法,gamma-delta(γδ)T 细胞近年来已被引入用于包括胶质母细胞瘤在内的多种癌症。由于 γδ T 细胞的主要作用是通过识别包括应激分子、磷酸抗原或脂质抗原在内的广泛配体来执行免疫监视,近期研究提示 γδ T 细胞转移对胶质母细胞瘤具有潜在益处。然而,γδ T 细胞作为人外周血 T 细胞中的一个小亚群(1-5%),与传统 alpha-beta(αβ)T 细胞相比相对未知。在此背景下,我们的研究引入 γδ T 细胞作为一种替代性且新颖的选择,以克服胶质母细胞瘤治疗中免疫细胞疗法面临的若干挑战。我们描述了 γδ T 细胞相较于传统 αβ T 细胞的独特特征和优势,并总结了近期使用人 gamma-delta T 细胞疗法治疗胶质母细胞瘤的若干临床前研究。最后,我们提出了人 γδ T 细胞疗法治疗胶质母细胞瘤的未来方向。
Glioblastoma is the most common brain malignancy with devastating prognosis. Numerous clinical trials using various target therapeutic agents have failed and recent clinical trials using check point inhibitors also failed to provide survival benefits for glioblastoma patients. Adoptive T cell transfer is suggested as a novel therapeutic approach that has exhibited promise in preliminary clinical studies. However, the clinical outcomes are inconsistent, and there are several limitations of current adoptive T cell transfer strategies for glioblastoma treatment. As an alternative cell therapy, gamma-delta (γδ) T cells have been recently introduced for several cancers including glioblastoma. Since the leading role of γδ T cells is immune surveillance by recognizing a broad range of ligands including stress molecules, phosphoantigens, or lipid antigens, recent studies have suggested the potential benefits of γδ T cell transfer against glioblastomas. However, γδ T cells, as a small subset (1-5%) of T cells in human peripheral blood, are relatively unknown compared to conventional alpha-beta (αβ) T cells. In this context, our study introduced γδ T cells as an alternative and novel option to overcome several challenges regarding immune cell therapy in glioblastoma treatment. We described the unique characteristics and advantages of γδ T cells compared to conventional αβ T cells and summarize several recent preclinical studies using human gamma-delta T cell therapy for glioblastomas. Finally, we suggested future direction of human γδ T cell therapy for glioblastomas.
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