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Expression patterns of immune checkpoints in acute myeloid leukemia

急性髓系白血病免疫检查点的表达模式

  • 影响因子:7.44
  • DOI:10.1186/s13045-020-00853-x
  • 作者列表:"Cunte Chen","Chaofeng Liang","Shunqing Wang","Chi Leong Chio","Yuping Zhang","Chengwu Zeng","Shaohua Chen","Caixia Wang","Yangqiu Li
  • 发表时间:2020-04-03
Abstract

Abstract Immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival. This type of therapy is still not available for acute myeloid leukemia (AML). One major issue is the lack of knowledge for the expression patterns of immune checkpoints (IC) in AML. In this study, we first explored the prognostic value of ICs for AML patients by analyzing RNA-seq and mutation data from 176 AML patients from the Cancer Genome Atlas (TCGA) database. We further validated the results of the database analysis by analyzing bone marrow (BM) samples from 62 patients with de novo AML. Both TCGA data and validation results indicated that high expression of PD-1, PD-L1, and PD-L2 was associated with poor overall survival (OS) in AML patients. In addition, increased co-expression of PD-1/CTLA-4 or PD-L2/CTLA-4 correlated with poor OS in AML patients (3-year OS: TGCA data 30% vs 0% and 20% vs 0%, validation group 57% vs 31% and 57% vs 33%, respectively) (P < 0.05). Moreover, co-expression of PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 was found to correlate with poor OS in AML patients with FLT3mut, RUNX1mut, and TET2mut, respectively. In conclusion, high expression of ICs in the BM leukemia cells of AML patients correlated with poor outcome. The co-expression patterns of PD-1/CTLA-4, PD-L2/CTLA-4, PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 might be potential immune biomarkers for designing novel AML therapy.

摘要

摘要免疫检查点抑制剂 (ICIs) 免疫治疗实体瘤的总生存率显著提高。这种类型的疗法仍然不能用于急性髓系白血病 (AML)。一个主要问题是缺乏 AML 中免疫检查点 (IC) 表达模式的知识。在本研究中,我们首先通过分析癌症基因组图谱 (TCGA) 数据库中 176 例 AML 患者的 RNA-seq 和突变数据,探讨了 ICs 对 AML 患者的预后价值。我们通过分析 62 例初治 AML 患者的骨髓 (BM) 样本,进一步验证了数据库分析的结果。TCGA 数据和验证结果均表明,PD-1 、 PD-L1 和 PD-L2 的高表达与 AML 患者的总生存期 (OS) 差相关。此外,AML 患者 PD-1/CTLA-4 或 PD-L2/CTLA-4 共表达增加与 OS 差相关 (3 年 OS: TGCA 数据 30% vs 0% 和 20% vs 0%,验证组分别为 57% vs 31% 和 57% vs 33%) (P <0.05)。此外,在患有 FLT3mut 、 RUNX1mut 和 TET2mut 的 AML 患者中,发现 PD-1/PD-L1 、 PD-1/PD-L1/PD-L2 和 PD-1/LAG-3 的共表达与 OS 差相关。分别。总之,AML 患者 BM 白血病细胞中 ICs 的高表达与不良预后相关。PD-1/CTLA-4 、 PD-L2/CTLA-4 、 PD-1/PD-L1 、 PD-1/LAG-3 可能是设计新型 AML 治疗的潜在免疫生物标志物。

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