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血液系统恶性肿瘤中的γδ T细胞:作用机制与治疗策略

γδ T cells in hematological malignancies: mechanisms and therapeutic strategies.

作者信息

Chen Xingchi, Sun Guangyu, Zhu Xiaoyu

机构信息

Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. Hefei, Anhui 230001, China.

Blood and Cell Therapy Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Hefei, Anhui 230001, China.

出版信息

Blood Sci. 2024 Dec 11;7(1):e00213. doi: 10.1097/BS9.0000000000000213. eCollection 2025 Jan.

Abstract

γδ T cells are a unique subset of lymphocytes with both innate and adaptive features. They recognize and eradicate various hematological malignancies through different mechanisms, employing factors including γδ TCR, NKR, NKG2D, TRAIL, and perforin/granzyme. They also modulate other immune cells to enhance their antitumor activity. Moreover, γδ T cells have potent antiviral functions after hematopoietic stem cell transplantation (HSCT), which may improve the outcome of patients with hematological malignancies. In this review, we summarize the current knowledge on γδ T cell biology and function in hematological malignancies and HSCT complications. We also discuss the challenges and limitations of the clinical application of γδ T cells, such as their low frequency in peripheral blood and heterogeneity among different subsets. We then highlight some promising strategies for γδ T cell-based therapy, such as using agonist antibodies, cell engagers, or genetic modification technology. Furthermore, we review the recent clinical trials evaluating the safety and efficacy of γδ T-cell therapy in different hematological malignancies. In conclusion, γδ T cells represent a promising immunotherapeutic tool for hematological malignancies that deserves further exploration.

摘要

γδ T细胞是一类具有先天和适应性特征的独特淋巴细胞亚群。它们通过不同机制识别并根除各种血液系统恶性肿瘤,所利用的因子包括γδT细胞受体、自然杀伤细胞受体、自然杀伤细胞2D、肿瘤坏死因子相关凋亡诱导配体以及穿孔素/颗粒酶。它们还可调节其他免疫细胞以增强其抗肿瘤活性。此外,γδ T细胞在造血干细胞移植(HSCT)后具有强大的抗病毒功能,这可能改善血液系统恶性肿瘤患者的预后。在本综述中,我们总结了目前关于γδ T细胞生物学及其在血液系统恶性肿瘤和HSCT并发症中的功能的知识。我们还讨论了γδ T细胞临床应用中的挑战和局限性,例如它们在外周血中的低频率以及不同亚群之间的异质性。然后,我们重点介绍了一些基于γδ T细胞疗法的有前景的策略,例如使用激动剂抗体、细胞衔接器或基因编辑技术。此外,我们回顾了最近评估γδ T细胞疗法在不同血液系统恶性肿瘤中的安全性和有效性的临床试验。总之,γδ T细胞是血液系统恶性肿瘤一种有前景的免疫治疗工具,值得进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8698/11637750/f613c8a90b3b/bs9-7-e00213-g001.jpg

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