肿瘤细胞治疗研究
英文原题：Translational potential of γδ T cells in hematologic diseases: from immunobiology to therapeutic innovation.
血液系统疾病，包括恶性和自身免疫性疾病，持续构成临床挑战，其特征为复发、治疗耐药和严重的免疫失调。
血液系统疾病，包括恶性和自身免疫性疾病，持续存在以复发、治疗耐药和严重免疫失调为特征的临床挑战。尽管传统免疫疗法已取得进展，但其疗效常受限于 HLA 下调和效应 T 细胞耗竭。在此背景下，γδ T 细胞提供了一种有前景的治疗替代方案。γδ T 细胞识别抗原不受 MHC 限制，具有内在的组织归巢能力，并表现出细胞毒性和免疫调节双重功能。这些特性使其非常适合作为异体“现货型”细胞疗法的候选者，而 αβ T 细胞在此面临同种异体反应性限制。本综述系统整合了 γδ T 细胞的免疫生物学，探讨特定亚群的功能异质性及其在肿瘤微环境（TME）中的调控。我们批判性评估了近期支持过继转移、CAR-γδ T 策略及联合方案用于急性白血病、淋巴瘤、多发性骨髓瘤和免疫性血细胞减少症的临床前和临床证据。此外，我们讨论了关键的转化障碍——包括体内持久性、亚群耗竭和制造变异性——并探讨了合理工程策略、代谢预处理和表观遗传调控作为解决方案。最终，推进 γδ T 细胞疗法需要克服这些障碍，使其有效地从实验室转化为主流临床实践。
Hematologic disorders, including malignant and autoimmune conditions, present persistent clinical challenges characterized by relapse, treatment resistance, and profound immune dysregulation. While conventional immunotherapies have advanced, their efficacy is frequently limited by HLA downregulation and effector T cell exhaustion. In this context, γδ T cells offer a promising therapeutic alternative. Recognizing antigens independently of MHC restriction, γδ T cells possess intrinsic tissue-homing capabilities and exhibit dual cytotoxic and immunoregulatory functions. These properties make them highly suitable candidates for allogeneic, "off-the-shelf" cellular therapies where αβ T cells face alloreactive limitations. This review systematically synthesizes the immunobiology of γδ T cells, exploring the functional heterogeneity of specific subsets and their regulation within the tumor microenvironment (TME). We critically evaluate recent preclinical and clinical evidence supporting adoptive transfer, CAR-γδ T strategies, and combination regimens across acute leukemias, lymphomas, multiple myeloma, and immune cytopenias. Furthermore, we address critical translational barriers-including in vivo persistence, subset exhaustion, and manufacturing variability-and discuss rational engineering strategies, metabolic preconditioning, and epigenetic modulation as solutions. Ultimately, advancing γδ T cell therapies requires overcoming these hurdles to transition them effectively from the bench to mainstream clinical practice.
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