Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Front Immunol. 2019 Aug 22;10:1997. doi: 10.3389/fimmu.2019.01997. eCollection 2019.
T-cell receptor (TCR) γδ cells are perceived as innate-like effector cells with the possibility of mediating graft-vs. -tumor (GVT) without causing graft-vs.-host disease (GVHD) in the setting of hematopoietic allogeneic stem cell transplantation (HSCT). We conducted a prospective study to assess the clinical impact of TCR γδ cell immune reconstitution on overall survival, relapse-free-survival, relapse and GVHD. The impact of CD3, CD4, and CD8 T cells together with NK cells including subtypes were analyzed in parallel. A total of 108 patients with hematological malignancies transplanted with HLA-matched, T cell replete stem cell grafts were included for analyses of absolute concentrations of CD3, CD4, and CD8 positive T cells and NK cells together with a multi-color flow cytometry panel with staining for TCRαβ, TCRγδ, Vδ1, Vδ2, CD3, CD4, CD8, HLA-DR, CD196, CD45RO, CD45RA, CD16, CD56, CD337, and CD314 at 28, 56, 91, 180, and 365 days after transplantation. Immune reconstitution data including subsets and differentiation markers of T and NK cells during the first year after transplantation was provided. Patients with TCR γδ cell concentrations above the median value of 21 (0-416) × 10 cells/L 56 days after transplantation had significantly improved overall survival ( = 0.001) and relapse-free survival ( = 0.007) compared to patients with concentrations below this value. When day 56 cell subset concentrations were included as continuous variables, TCR γδ cells were the only T cell subsets with a significant impact on OS and RFS; the impact of TCR γδ cells remained statistically significant in multivariate analyses adjusted for pre-transplant risk factors. The risk of death from relapse was significantly decreased in patients with high concentrations of TCR γδ cells 56 days after transplantation ( = 0.003). Also, the risk of acute GVHD was significantly lower in patients with day 28 TCR γδ cell concentrations above the median of 18 × 10 cells/L compared to patients with low concentrations ( = 0.01). These results suggest a protective role of TCR γδ cells in relapse and GVHD and encourage further research in developing adaptive TCR γδ cell therapy for improving outcomes after HSCT.
T 细胞受体 (TCR) γδ 细胞被认为是具有先天样效应细胞的可能性，可在造血干细胞移植 (HSCT) 中介导移植物抗宿主病 (GVHD) 而不引起移植物抗宿主病 (GVHD)。我们进行了一项前瞻性研究，以评估 TCR γδ 细胞免疫重建对总生存、无复发生存、复发和 GVHD 的临床影响。同时分析了 CD3、CD4 和 CD8 T 细胞以及 NK 细胞(包括亚型)的影响。共纳入 108 例接受 HLA 匹配、T 细胞丰富的干细胞移植的血液系统恶性肿瘤患者，分析 CD3、CD4 和 CD8 阳性 T 细胞和 NK 细胞的绝对浓度，同时使用多色流式细胞术分析 TCRαβ、TCRγδ、Vδ1、Vδ2、CD3、CD4、CD8、HLA-DR、CD196、CD45RO、CD45RA、CD16、CD56、CD337 和 CD314，在移植后 28、56、91、180 和 365 天进行检测。提供了移植后第一年 T 和 NK 细胞的亚群和分化标志物的免疫重建数据。与浓度低于该值的患者相比，移植后 56 天 TCR γδ 细胞浓度高于中位数 21(0-416)×10 细胞/L 的患者具有显著改善的总生存(=0.001)和无复发生存(=0.007)。当将第 56 天细胞亚群浓度作为连续变量时，TCR γδ 细胞是唯一对 OS 和 RFS 有显著影响的 T 细胞亚群;在调整移植前危险因素的多变量分析中，TCR γδ 细胞的影响仍然具有统计学意义。移植后 56 天 TCR γδ 细胞浓度高的患者死于复发的风险显著降低(=0.003)。此外，与浓度较低的患者相比，第 28 天 TCR γδ 细胞浓度高于中位数 18×10 细胞/L 的患者发生急性 GVHD 的风险显著降低(=0.01)。这些结果表明 TCR γδ 细胞在复发和 GVHD 中具有保护作用，并鼓励进一步研究开发适应性 TCR γδ 细胞疗法，以改善 HSCT 后的结果。
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