CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于基因特征的急性髓系白血病预后模型：BATF、EGR1、PD-1、PD-L1 和 TIM-3 的作用
英文原题：Gene Signature-Based Prognostic Model for Acute Myeloid Leukemia: The Role of BATF, EGR1, PD-1, PD-L1, and TIM-3.
查看英文原题
Gene Signature-Based Prognostic Model for Acute Myeloid Leukemia: The Role of BATF, EGR1, PD-1, PD-L1, and TIM-3.
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中文摘要
背景
急性髓系白血病（AML）是一种造血干/祖细胞恶性肿瘤，T细胞耗竭与不良结局相关。既往研究显示，碱性亮氨酸拉链ATF样转录因子（BATF）和早期生长反应因子1（EGR1）参与AML肿瘤清除过程中CAR-T 细胞耗竭，但二者在AML预后中的作用及其与免疫检查点基因的关系尚未充分研究。
方法
分析本中心92例初诊AML患者骨髓样本（JUN数据集）中的BATF、EGR1、程序性细胞死亡蛋白1（PD-1）、程序性死亡配体1（PD-L1）及T细胞免疫球蛋白和黏蛋白结构域蛋白3（TIM3）表达，并评估预后。另使用TCGA数据库155例和Beat-AML数据库199例患者的RNA测序数据进行验证。
结果
BATF高表达与较差总生存期（OS）相关（P=.030），EGR1高表达则提示预后较好（P=.040）。BATF高表达且EGR1低表达患者结局最差（P<.001）。在接受异基因造血干细胞移植（allo-HSCT）的患者中，BATF高表达与较短OS相关（P=.004）。结合BATF、EGR1、PD-1、PD-L1和TIM-3构建的预后模型可计算风险评分；在全体AML患者及allo-HSCT受者中，高危患者OS均显著短于低危患者（P<.001）。TCGA和Beat-AML数据集也得到相似结果。
结论
本研究建立了基于BATF、EGR1、PD-1、PD-L1和TIM-3表达的预后模型，可有效预测AML患者及allo-HSCT受者的生存结局，有望为预后评估和治疗策略提供参考。
展开英文摘要原文
Background: Acute myeloid leukemia (AML) is a malignancy of hematopoietic stem and progenitor cells, with T cell exhaustion linked to poor outcomes.
Our previous research has shown that basic leucine zipper ATF-like transcription factor ( BATF ) and early growth response 1 ( EGR1 ) play a role in chimeric antigen receptor T (CAR-T) cell exhaustion during AML tumor elimination.
However, the roles of BATF and EGR1 and their association with immune checkpoint genes in AML prognosis remain underexplored. Methods: Bone marrow (BM) samples from 92 newly diagnosed AML patients at our clinical center (JUN-dataset) were analyzed to detect the expression levels of BATF , EGR1 , programmed cell death 1 ( PD-1 ), programmed death-ligand 1 ( PD-L1 ), T cell immunoglobulin and mucin domain-containing protein 3 ( TIM3 ) together with conducting a prognostic assessment.
Our findings were validated using RNA sequencing data from 155 AML patients from the TCGA database and 199 AML patients from the Beat-AML database. Results: High BATF expression correlated with poor overall survival (OS) ( P = 0. 030), whereas high EGR1 expression indicated a favorable prognosis ( P = 0. 040). Patients with high BATF and low EGR1 expression had worst outcomes ( P < 0. 001). Among those receiving allogenic hematopoietic stem cell transplantation (allo-HSCT), high BATF expression was linked to shorter OS ( P = 0. 004).
Moreover, a prognostic model incorporating BATF , EGR1 , PD-1 , PD-L1 , and TIM-3 calculated a risk score, with high-risk patients demonstrating significantly shorter OS than low-risk patients in both total AML patients and allo-HSCT recipients ( P < 0. 001). Similar results were found in both the TCGA and Beat-AML datasets.
Conclusions: We establish a prognostic model based on BATF , EGR1 , PD-1 , PD-L1 , and TIM-3 expression that effectively predicts survival outcomes for AML patients and allo-HSCT recipients. This model may provide valuable insights for prognosis assessment and treatment strategies.
论文信息
- 作者
- Zhang Y、Chen Z、Zheng J、Chen S、Zhong L、Chen J、Chen C、Sui S
- 单位
- Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, China.China
- 期刊
- International journal of medical sciences2025
- 原文标识
- PubMed 40225861 · DOI 10.7150/ijms.108527
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