急性髓系白血病粘膜相关不变 T 细胞的免疫特征和预后意义。
Immune characteristics and prognostic implications of mucosal-associated invariant T cells in acute myeloid leukemia.
发表日期:2023 Nov 06
作者:
Qian Peng, Renhua Huang, Huiping Wang, Hao Xiao, Yiping Wang, Zhimin Zhai, Zhitao Wang
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
越来越多的证据表明,粘膜相关不变 T 细胞 (MAIT) 在针对各种癌症的抗肿瘤反应中发挥着至关重要的作用。在本研究中,我们研究了急性髓系白血病(AML)患者 MAIT 细胞的免疫特征。使用多参数流式细胞术,我们对 131 例 AML 患者(包括 99 例新诊断病例、18 例缓解病例和 14 例复发病例)以及 69 例健康对照采集的外周血或骨髓样本中的 MAIT 进行表型和功能分析。我们发现 MAIT 在新诊断时表现出衰老和疲惫的迹象,特别是在 CD8 MAIT 子集中。 MAIT 表现出效应记忆或终末分化表型。 MAIT 的频率和数量反映了 AML 细胞遗传特征、肿瘤负荷、疾病状态和治疗反应。此外,MAIT 表现出高度激活甚至耗尽状态,如 PD-1 上调所示。此外,在 AML 患者的 MAIT 中观察到 Th1 型细胞因子的产生受损,而 Th17 型细胞因子、颗粒酶 B 和穿孔素的分泌增加。此外,MAIT 转向产生促进肿瘤进展的细胞因子,例如 IL-8。 MAITs 频率较低与总生存期 (OS) 较差相关,多变量分析显示 MAITs 频率<<2.12% 是影响 OS 的独立预后因素。总的来说,我们的研究结果表明 MAIT 可能在 AML 免疫缺陷中发挥作用,强调了它们在 AML 发病机制和治疗中的潜在重要性。这些发现为 AML 中新型免疫治疗策略的开发提供了理论基础。© 2023。作者获得 Springer-Verlag GmbH 德国(Springer Nature 旗下公司)的独家许可。
Increasing evidence suggests that mucosal-associated invariant T cells (MAITs) play a crucial role in anti-tumor responses against various cancers. In this study, we investigated the immune characteristics of MAIT cells in patients with acute myeloid leukemia (AML). Using multi-parameter flow cytometry, we performed phenotypic and functional analysis of MAITs in peripheral blood or bone marrow samples collected from 131 patients with AML including 99 newly diagnosed, 18 remission, and 14 relapsed cases, as well as 69 healthy controls. We found that MAITs exhibit signs of aging and exhaustion, particularly in CD8+ MAITs subset, at newly diagnosis. MAITs exhibit an effector memory or terminally differentiated phenotype. Frequency and number of MAITs reflect AML cell genetic features, tumor burden, disease status, and treatment responsiveness. Moreover, MAITs exhibit a highly activated or even exhausted state, as indicated by upregulation of PD-1. Furthermore, impaired production of Th1-type cytokines and increased secretion of Th17-type cytokines, granzyme B, and perforin were observed in MAITs from AML patients. Additionally, MAITs shifted toward producing cytokines that promote tumor progression, such as IL-8. Lower frequency of MAITs was associated with poorer overall survival (OS), and multivariate analysis revealed that MAITs frequency < 2.12% was an independent prognostic factor affecting OS. Collectively, our findings suggest that MAITs may play a role in immune deficiency in AML, emphasizing their potential importance in AML pathogenesis and treatment. These discoveries provide a theoretical basis for the development of novel immunotherapeutic strategies in AML.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.