Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou 510632, China.
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China.
Biomed Res Int. 2020 Jul 27;2020:4612952. doi: 10.1155/2020/4612952. eCollection 2020.
Foxp3+ regulatory T ( 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+ Treg cell subsets in acute myeloid leukemia (AML) patients of different clinical statuses: AML (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+ T cells are significantly higher in and NR patients. High levels of TIGIT and DNAM-1 on Foxp3+ T cells correlated with increased Foxp3+ T cell frequencies. In addition, a high TIGIT/DNAM-1 ratio was observed in AML patients and healthy individuals (HIs). Furthermore, the phenotypic abnormalities in Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ T cells were restored when the patients achieved CR after chemotherapy. Moreover, higher TIGIT+Foxp3+ 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+ Treg cells and indicates the clinical progression and prognosis of AML patients of different clinical statuses, which is considered beneficial for efficient AML immunotherapy.
Foxp3+ 调节性 T（Treg）细胞通过多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 细胞免疫球蛋白和 ITIM 结构域（TIGIT）与共刺激受体 DNAX 辅助分子 1（DNAM-1）具有相似的配体，并抑制肿瘤患者的 T 细胞反应。本研究旨在研究 TIGIT/DNAM-1 轴是否参与不同临床状态的急性髓系白血病（AML）患者 Foxp3+Treg 细胞亚群的分布和表达：AML（27 例）、未缓解（NR）的 AML（7 例）和完全缓解（CR）的 AML（12 例）。我们的数据表明，和 NR 患者中 Foxp3+、TIGIT+Foxp3+和 DNAM-1+Foxp3+T 细胞的比例明显更高。Foxp3+T 细胞上高水平的 TIGIT 和 DNAM-1 与 Foxp3+T 细胞频率增加相关。此外，在 AML 患者和健康个体（HIs）中观察到高 TIGIT/DNAM-1 比值。此外，当患者在化疗后达到 CR 时，Foxp3+、TIGIT+Foxp3+和 DNAM-1+Foxp3+T 细胞的表型异常得到恢复。此外，较高的 TIGIT+Foxp3+T 细胞与 AML 患者的总生存不良相关，是预后的独立危险因素。总之，本研究首次揭示 TIGIT/DNAM-1 轴可能参与 Foxp3+Treg 细胞，并表明不同临床状态的 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。
