Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.

最近，许多发现阐明了白血病微环境中的细胞和分子多样性，并提高了我们对其复杂性质的认识。这使得开发针对白血病的新治疗策略成为可能。生物技术的进步和目前对 T 细胞工程的理解为这场斗争带来了新的方法，从而改善了细胞介导的抗癌免疫反应。然而，大多数研究只关注传统的细胞毒性细胞，而忽略了迄今为止鲜有研究的非常规 T 细胞的潜力。γδ T 细胞是一种独特的淋巴细胞亚群，具有广泛的肿瘤传感功能，可能在广泛的肿瘤中具有新的免疫治疗应用。无论人类白细胞抗原 (HLA) 表达、抗肿瘤介质的分泌和高功能可塑性如何，都能够做出反应，这是 γδ T 细胞的标志，并使它们成为细胞治疗领域有前景的替代品。尽管存在这种情况，但在特定情况下，白血病微环境可以采取策略来规避这些淋巴细胞的抗肿瘤反应，导致它们衰竭或分化为促肿瘤表型。干预这种串扰可以提高他们的能力和临床应用，并使他们成为新的抗白血病治疗方法的关键组成部分。在这篇综述中，我们重点介绍了 γδ T 细胞的几个特征及其在白血病中的相互作用。此外，我们探索了最大化其抗肿瘤功能的策略，旨在说明旨在更好地动员γδ T细胞对抗肿瘤的发现。最后，我们概述了我们对其治疗适用性的看法，并指出了未来白血病基础和临床研究的突出问题，希望为癌症免疫治疗中γδT细胞研究的进步做出贡献。