胶质母细胞瘤是最常见的脑恶性肿瘤，预后令人绝望。许多采用不同目标治疗药物的临床试验均以失败告终，最近使用免疫检查点抑制剂进行的临床试验同样未能为胶质母细胞瘤患者提供生存益处。移植性T细胞转移被建议为一种新型疗法，初步的临床研究显示了其潜力。然而，临床结果不一致，并且当前的移植性T细胞转移策略在胶质母细胞瘤治疗中存在几个局限性。作为另一种细胞疗法，γδT细胞最近被引入用于多种癌症，包括胶质母细胞瘤。由于γδT细胞的主要作用是通过识别一系列配体，包括应激分子、磷酸抗原或脂质抗原，进行免疫监视，最近的研究表明了γδT细胞转移对胶质母细胞瘤的潜在益处。然而，相对于常规的αβT细胞，γδT细胞作为人类外周血中的一小部分（1-5%）尚未被广泛了解。在这种背景下，我们的研究介绍了γδT细胞作为克服胶质母细胞瘤免疫细胞治疗中的几个挑战的替代和新选择。我们描述了γδT细胞与常规αβT细胞相比的独特特性和优势，并总结了几个最近使用人类γδT细胞疗法治疗胶质母细胞瘤的临床前研究。最后，我们提出了后续人类γδT细胞疗法在胶质母细胞瘤治疗中的未来方向。版权所有©2023年Elsevier B.V.出版。

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.Copyright © 2023. Published by Elsevier B.V.