PDF(Pubmed)
Abstract：
Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied in these therapies have proven efficacy but are confined almost exclusively to autologous use. When infused into patients with mismatched human leukocyte antigen, αβ T cells recognize tissues of such patients as foreign and elicit devastating graft-versus-host disease. Therefore, one way to overcome this challenge is to use naturally allogeneic immune cell types, such as γδ T cells. γδ T cells occupy the interface between innate and adaptive immunity and possess the capacity to detect a wide variety of ligands on transformed host cells. In this article, we review the fundamental biology of γδ T cells, including their subtypes, expression of ligands, contrasting roles in and association with cancer prognosis or survival, as well as discuss the gaps in knowledge pertaining to this cell type which we currently endeavor to elucidate. In addition, we propose how to harness the unique properties of γδ T cells for cellular immunotherapy based on lessons gleaned from past clinical trials and provide an update on ongoing trials involving these cells. Lastly, we elaborate strategies that have been tested or can be explored to improve the anti-tumor activity and durability of γδ T cells in vivo.
摘要：
过继性细胞免疫疗法作为治疗癌症的新范例，近年来FDA批准了针对血液恶性肿瘤的六种嵌合抗原受体-T细胞疗法。在这些疗法中应用的常规αβT细胞已被证明具有功效，但几乎仅限于自体使用。当输注给人类白细胞抗原不匹配的患者时，αβT细胞将这些患者的组织识别为外来的并引发破坏性的移植物抗宿主病。因此,克服这一挑战的一种方法是使用天然同种异体免疫细胞类型，如γδT细胞。γδT细胞占据先天免疫和适应性免疫之间的界面，并具有检测转化宿主细胞上多种配体的能力。在这篇文章中,我们回顾了γδT细胞的基本生物学，包括它们的亚型，配体的表达，在癌症预后或生存中的作用和关联，以及讨论我们目前正在努力阐明的与这种细胞类型有关的知识差距。此外,我们提出了如何利用γδT细胞的独特特性进行细胞免疫疗法的经验教训从过去的临床试验收集,并提供了有关这些细胞正在进行的试验的最新情况.最后,我们详细阐述了已经过测试或可以探索的策略，以提高体内γδT细胞的抗肿瘤活性和耐久性。
