Xie Dai-Hong, Wang Jun, Sun Kai, Shi Zong-Yan, Wang Ya-Zhe, Chang Yan, Yuan Xiao-Ying, Liu Yan-Rong, Jiang Hao, Jiang Qian, Huang Xiao-Jun, Qin Ya-Zhen
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
Biomedicines. 2024 Sep 27;12(10):2207. doi: 10.3390/biomedicines12102207.
: The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. : Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56, and CD56 NK cell subsets after in vitro stimulation. : The frequencies of TIGIT cells in total NK, CD56, and CD56 NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT cells than the corresponding TIGIT cells in all HDs, whereas those for TIGIT to TIGIT cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients' TIGIT NK cells displayed lower K562 cell-killing activity than their TIGIT NK cells. In addition, high frequencies of TIGIT cells in total NK and CD56 NK cells were associated with poor RFS. : TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.
新发现的免疫检查点——T细胞免疫球蛋白和基于免疫受体酪氨酸的抑制基序结构域（TIGIT）在核心结合因子急性髓系白血病（CBF-AML）中对自然杀伤（NK）细胞的影响仍有待研究。共收集了39例新诊断的CBF-AML患者和25名健康供者（HD）的新鲜骨髓样本，用于检测体外刺激后总NK、CD56⁺和CD56⁻NK细胞亚群的表型和功能状态。患者和HD的总NK、CD56⁺和CD56⁻NK细胞亚群中TIGIT⁺细胞的频率无显著差异。所有HD中，TIGIT⁺细胞的TNF-α和INF-γ水平均低于相应的TIGIT⁻细胞，而患者中TIGIT⁺细胞与TIGIT⁻细胞的水平高度异质性；HD中TIGIT表达与穿孔素（PFP）和颗粒酶B（GZMB）表达无关，而在患者中TIGIT表达与细胞内较高的PFP和GZMB水平相关。患者的TIGIT⁺NK细胞对K562细胞的杀伤活性低于其TIGIT⁻NK细胞。此外，总NK和CD56⁺NK细胞中TIGIT⁺细胞的高频率与无复发生存期（RFS）差相关。TIGIT表达影响诊断时骨髓部位NK细胞功能，对CBF-AML患者具有预后意义。
