急性髓系白血病（AML）仍然是一个难以治疗甚至治愈的疾病，即使经过包括干细胞移植在内的高强度疗法。基于常规的αβT细胞的养育细胞治疗策略在髓系肿瘤研究中是一个活跃的领域，因为它们在其他血液肿瘤中取得了显著的成功，特别是B细胞来源的急性淋巴细胞白血病、骨髓瘤和淋巴瘤。数个限制因素阻碍了养育细胞治疗在AML中的临床应用，包括缺乏白血病特异性抗原、对靶抗原和白血病细胞的毒性、免疫抑制微环境以及难以免疫识别和摧毁的白血病干细胞种群。虽然有一些正在开发中的基于T细胞的治疗方法，包括嵌合抗原受体（CAR-T）设计，但其他细胞毒性淋巴细胞亚群具有独特的表型和功能，可能对AML治疗有额外的益处。特别感兴趣的是自然杀伤细胞（NK）和非常规T细胞，即不变自然杀伤T细胞（iNKT）和γδT细胞。NK、iNKT和γδT细胞表现出固有的抗恶性特性、异基因反应性潜力以及与人类白细胞抗原（HLA）无关的功能。本文回顾了这些非常规细胞毒性淋巴细胞类型的生物学，并比较和对比它们的优势和局限性，作为AML养育细胞治疗的基础。版权所有© 2023 Kent, Crump and Davila.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immunosuppressive microenvironments, and leukemic stem cell populations elusive to immune recognition and destruction. While there are promising T cell-based therapies including chimeric antigen receptor (CAR)-T designs under development, other cytotoxic lymphocyte cell subsets have unique phenotypes and capabilities that might be of additional benefit in AML treatment. Of particular interest are the natural killer (NK) and unconventional T cells known as invariant natural killer T (iNKT) and gamma delta (γδ) T cells. NK, iNKT, and γδT cells exhibit intrinsic anti-malignant properties, potential for alloreactivity, and human leukocyte-antigen (HLA)-independent function. Here we review the biology of each of these unconventional cytotoxic lymphocyte cell types and compare and contrast their strengths and limitations as the basis for adoptive cell therapies for AML.Copyright © 2023 Kent, Crump and Davila.