CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD8+ T 细胞的克隆扩增反映了移植物抗白血病活性，并在 DLI 后持久缓解之前出现
英文原题：Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI.
查看英文原题
Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI.
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中文摘要
供者淋巴细胞输注（DLI）是异基因造血干细胞移植后急性髓系白血病复发的标准治疗。目前，对于CD8+ αβ T细胞在DLI后如何以及何时发挥移植物抗白血病（GVL）活性，人们知之甚少。
此外，尚无可靠的生物标志物来监测输注的CD8+ T细胞的GVL活性。因此，我们分析了DLI患者中CD8+ αβ T细胞克隆的动态变化。在这项纳入29例患者的前瞻性临床研究中，我们对分选后的CD8+ αβ T细胞进行了T细胞受体β（TRB）深度测序，以追踪患者对DLI应答的免疫组库变化。在GVL首次出现时，纵向分析显示特定CD8+TRB克隆出现优先扩增（n = 14）。这在无GVL迹象的患者样本中未出现（n = 11）。
重要的是，DLI后15天的早期免疫组库变化预测了36个月研究随访期间的持久缓解。此外，DLI后CD8+TRB免疫组库无克隆性扩增是一个早期生物标志物，可在实际诊断前中位11.2个月预测复发。
另外，无论临床结局如何，对样本进行无偏分析显示，DLI后第15天CD8+TRB多样性下降的患者（n = 13）与无克隆扩增的患者（n = 6）相比，复发发生率更低（P = .0040）。
总之，CD8+TRB分析可能为预测DLI疗效提供可靠工具，并有望识别DLI后存在疾病进展和复发风险的患者。
展开英文摘要原文
Donor lymphocyte infusion (DLI) is a standard of care for relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GVL) activity after DLI. Also, there is no reliable biomarker to monitor GVL activity of the infused CD8+ T cells.
Therefore, we analyzed the dynamics of CD8+ αβ T-cell clones in patients with DLI. In this prospective clinical study of 29 patients, we performed deep T-cell receptor β (TRB ) sequencing of sorted CD8+ αβ T cells to track patients' repertoire changes in response to DLI. Upon first occurrence of GVL, longitudinal analyses revealed a preferential expansion of distinct CD8+TRB clones (n = 14). This did not occur in samples of patients without signs of GVL (n = 11).
Importantly, early repertoire changes 15 days after DLI predicted durable remission for the 36-month study follow-up.
Furthermore, absence of clonal outgrowth of the CD8+TRB repertoire after DLI was an early biomarker that predicted relapse at a median time of 11. 2 months ahead of actual diagnosis.
Additionally, unbiased sample analysis regardless of the clinical outcome revealed that patients with decreasing CD8+TRB diversity at day 15 after DLI (n = 13) had a lower relapse incidence (P = . 0040) compared with patients without clonal expansion (n = 6).
In conclusion, CD8+TRB analysis may provide a reliable tool for predicting the efficacy of DLI and holds the potential to identify patients at risk for progression and relapse after DLI.
论文信息
- 作者
- Schultze-Florey CR、Kuhlmann L、Raha S、Barros-Martins J、Odak I、Tan L、Xiao Y、Ravens S
- 单位
- Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, and.
- 文献类型
- 非美国政府资助研究
- 期刊
- Blood advances2021 Nov 9
- 原文标识
- PubMed 34535011 · DOI 10.1182/bloodadvances.2020004073
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