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首页> 外文期刊>Cellular immunology >TIGIT expression is upregulated in T cells and causes T cell dysfunction independent of PD-1 and Tim-3 in adult B lineage acute lymphoblastic leukemia
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TIGIT expression is upregulated in T cells and causes T cell dysfunction independent of PD-1 and Tim-3 in adult B lineage acute lymphoblastic leukemia

机译：TIGIT表达在T细胞中上调，使T细胞功能障碍无关，无论是PD-1和TIM-3在成人B谱系急性淋巴细胞白血病中

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摘要

T cell immunoglobulin and ITIM domain (TIGIT) is a novel immune checkpoint receptor and plays critical roles in cancer immunity. Adult acute lymphoblastic leukemia (ALL) remains a treatment challenge despite years of research. In this study, we analyzed the status of TIGIT expression in circulating T cells from patients with adult ALL. Compared to the data in healthy controls, the expression of TIGIT in CD4(+)CD25(-) T cells and CD8(+) T cells in adult ALL patients presented a small but significant upregulation. Stimulation via the CD3/CD28 route increased TIGIT mRNA expression at 24 h, which peaked at 48 h and was maintained at 72 h post-stimulation. The frequency of TIGIT(+) cells, on the other hand, consistently increased over time. ALL protein lysate or Wilms' Tumor 1 peptide could significantly increase the expression of TIGIT in ALL, but not healthy control T cells. Compared to TIGIT- cells, the TIGIT+ cells presented significantly higher PD-1 and Tim-3 expression directly ex vivo, and significantly lower IL-2, IFN-gamma, and TNF-alpha after CD3/CD28 stimulation. The high inhibitory molecule and low cytokine expression signature was especially pronounced in ALL TIGIT(+) CD4(+)CD25(-) T cells and TIGIT(+) CD8(+) T cells. Blocking TIGIT alone could minimally increase cytokine expression independent of PD-1 and Tim-3 blocking, whereas blocking TIGIT, PD-1, and Tim-3 altogether was significantly more effective. Together, these data demonstrated that TIGIT regulated T cell function in adult ALL patients, and may serve as a treatment target for ALL.
机译：T细胞免疫球蛋白和ITIM结构域（TIGIT）是一种新的免疫检查点受体，并在癌症免疫中发挥关键作用。尽管有多年的研究，成人急性淋巴细胞白血病（全部）仍然是治疗挑战。在这项研究中，我们分析了成年患者循环T细胞中TIGIT表达的状态。与健康对照中的数据相比，成人中CD4（+）CD25（ - ）T细胞和CD8（+）T细胞中TIGIT的表达所有患者均呈现出小但重要的上调。通过CD3 / CD28的刺激途径增加了24小时的TIGIT mRNA表达，其在48小时达到峰值，并在刺激后72小时保持。另一方面，Tigit（+）细胞的频率随着时间的推移而持续增加。所有蛋白质裂解物或Wilms的肿瘤1肽可以显着增加所有蛋白质催泪肽在所有情况下都会显着增加TIGIT的表达，但不健康的对照T细胞。与TIGIT-细胞相比，TIGIT +细胞直接呈现出明显较高的PD-1和TIM-3表达，并且在CD3 / CD28刺激后显着降低IL-2，IFN-GAMMA和TNF-α。在所有TIGIT（+）CD4（+）CD25（ - ）T细胞和TIGIT（+）CD8（+）T细胞中，高抑制分子和低细胞因子表达签名特别明显。单独阻断TIGIT可以最小地增加细胞因子表达，而不独立于PD-1和TIM-3阻挡，而阻塞TIGIT，PD-1和TIM-3完全明显更有效。这些数据在一起表明，TIGIT规范的T细胞功能在成人中所有患者，也可以作为所有人的治疗目标。

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