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
调控急性髓系白血病中 CAR-T 细胞耗竭与适应性：代谢与微环境机制策略
英文原题：Modulating CAR-T cell exhaustion and fitness in acute myeloid leukemia: mechanistic metabolic and microenvironmental strategies.
查看英文原题
Modulating CAR-T cell exhaustion and fitness in acute myeloid leukemia: mechanistic metabolic and microenvironmental strategies.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
嵌合抗原受体（CAR）T细胞疗法在B细胞恶性肿瘤中取得了变革性成果，但在急性髓系白血病（AML）中仍受限，抗原异质性、髓系驱动的抑制性微环境以及代谢受限的骨髓龛共同损害了疗效。在AML中，CAR-T 细胞失败不仅由抗原逃逸驱动，还由涵盖转录、表观遗传、代谢和功能失调的协调性耗竭程序所驱动。AML骨髓龛通过抑制性免疫细胞群、抑制性细胞因子、检查点信号、代谢竞争和转运受损进一步强化功能障碍。本综述概述了一个“适应性优先”框架，整合了CAR-T 细胞性能的内在和外在决定因素。优化的生产、细胞编程和微环境调控提供了统一策略，以增强CAR-T 细胞适应性并在AML中实现持久治疗反应。
展开英文摘要原文
Chimeric antigen receptor (CAR) T-cell therapy has achieved transformative outcomes in B-cell malignancies but remains limited in acute myeloid leukemia (AML), where antigenic heterogeneity, a suppressive myeloid-driven microenvironment, and a metabolically restrictive bone marrow niche collectively impair efficacy. In AML, CAR T-cell failure is driven not only by antigen escape but by a coordinated program of exhaustion encompassing transcriptional, epigenetic, metabolic, and functional dysfunction.
The AML bone marrow niche further enforces dysfunction through suppressive immune populations, inhibitory cytokines, checkpoint signaling, metabolic competition, and impaired trafficking. This review outlines a "fitness-first" framework consolidating intrinsic and extrinsic determinants of CAR T-cell performance. Optimized manufacturing, cellular programming, and microenvironmental modulation provide a unified strategy to enhance CAR T-cell fitness and enable durable therapeutic responses in AML.
论文信息
- 作者
- Atilla E
- 单位
- Division of Transplantation and Cellular Therapy, Sylvester Comprehensive Cancer Center, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, United States.United States
- 文献类型
- 综述
- 期刊
- Frontiers in immunology2026
- 原文标识
- PubMed 42440668 · DOI 10.3389/fimmu.2026.1863485
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →