Characteristic of TIGIT and DNAM-1 Expression on Foxp3+γδ T Cells in AML Patients
Characteristic of TIGIT and DNAM-1 Expression on Foxp3+γδ T Cells in AML Patients
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AML患者Foxp3 γ δ T细胞TIGIT和DNAM-1表达特征
DOI：
10.1155/2020/4612952
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发表时间：
2020-07-27
影响因子：
--
通讯作者：
Wu, Xiuli
中科院分区：
文献类型：
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作者：
Jin, Zhenyi;Ye, Wanyi;Wu, Xiuli
Foxp 3 + γ δ调节性T（γ δ Treg）细胞通过各种机制促进肿瘤生长并诱导免疫衰老。新型免疫检查点共抑制受体T细胞IG和ITIM结构域（TIGIT）与共刺激受体DNAX辅助分子1（DNAM-1）共享相似的配体，并抑制肿瘤患者的T细胞应答。本研究旨在表征TIGIT/DNAM-1轴是否参与不同临床状态的急性髓性白血病（AML）患者中Foxp 3 + γ δ Treg细胞亚群的分布和表达：初治AML（27名患者）、未缓解的AML（NR）（7名患者）和完全缓解的AML（CR）（12名患者）。我们的数据表明，Foxp 3+、TIGIT+ Foxp 3+和DNAM-1+ Foxp 3 + γ δ T细胞的比例在初治和NR患者中显著更高。Foxp 3 + γ δ T细胞上的高水平TIGIT和DNAM-1与增加的Foxp 3 + γ δ T细胞频率相关。此外，在初治AML患者和健康个体（HI）中观察到高TIGIT/DNAM-1比率。此外，当患者在化疗后达到CR时，Foxp 3+、TIGIT+ Foxp 3+和DNAM-1+ Foxp 3 + γ δ T细胞的表型异常恢复。此外，较高的TIGIT+ Foxp 3 + γ δ T细胞与总体存活率差的AML患者相关，并且是预后的独立风险因素。总之，我们的研究首次揭示了TIGIT/DNAM-1轴可能参与Foxp 3 +gamma delta Treg细胞，并指示了不同临床状态的AML患者的临床进展和预后，这被认为有利于有效的AML免疫治疗。
Foxp3+gamma delta regulatory T (gamma delta Treg) cells promote tumor growth by various mechanisms and induce immuno-senescence. The novel immune checkpoint coinhibitory receptor T cell Ig and ITIM domain (TIGIT) shares similar ligands as the costimulatory receptor DNAX accessory molecule 1 (DNAM-1) and suppresses T cell responses in tumor patients. This study is aimed at characterizing whether the TIGIT/DNAM-1 axis is involved in the distribution and expression of Foxp3+gamma delta Treg cell subsets in acute myeloid leukemia (AML) patients of different clinical statuses:de novoAML (27 patients), AML in nonremission (NR) (7 patients), and AML in complete remission (CR) (12 patients). Our data demonstrated that the proportions of Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+gamma delta T cells are significantly higher inde novoand NR patients. High levels of TIGIT and DNAM-1 on Foxp3+gamma delta T cells correlated with increased Foxp3+gamma delta T cell frequencies. In addition, a high TIGIT/DNAM-1 ratio was observed inde novoAML patients and healthy individuals (HIs). Furthermore, the phenotypic abnormalities in Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+gamma delta T cells were restored when the patients achieved CR after chemotherapy. Moreover, higher TIGIT+Foxp3+gamma delta T cells were associated with AML patients who had poor overall survival and were an independent risk factor for prognosis. In conclusion, our study reveals for the first time that the TIGIT/DNAM-1 axis may be involved in Foxp3+gamma delta Treg cells and indicates the clinical progression and prognosis of AML patients of different clinical statuses, which is considered beneficial for efficient AML immunotherapy.