不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
调控衰老人群 CD8⁺ T 细胞衰老的非年龄依赖且可靶向的转录因子网络
英文原题：Age-independent and targetable transcription factor networks regulating CD8(+) T cell senescence in aging humans.
查看英文原题
Age-independent and targetable transcription factor networks regulating CD8(+) T cell senescence in aging humans.
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
免疫功能随年龄增长而下降，并伴随衰老CD8⁺ T细胞积累。本研究通过分离衰老细胞并结合多组学分析发现，无论供者年龄较轻还是较大，细胞向衰老状态转变均由染色质状态特异的转录因子（TF）网络调控。该网络广泛重塑增强子，抑制细胞身份相关基因，同时上调炎症和分泌通路。抑制或下调AP1、KLF5或RUNX2可调节转录输出，并部分恢复衰老CD8⁺ T细胞对刺激反应减弱的状态。衰老CD8⁺ T细胞基因特征还可预测弥漫大B细胞淋巴瘤患者对嵌合抗原受体（CAR）T细胞疗法的应答。总体而言，本研究界定了人CD8⁺ T细胞衰老背后的基因调控机制，指出扰动TF网络是调节衰老状态的可行策略，并确定衰老CD8⁺ T细胞基因特征可作为预测免疫治疗结局的工具。
展开英文摘要原文
The age-related decline in immunity is accompanied by the accumulation of senescent CD8 + T cells. Using senescent cell isolation coupled with multi-omics profiling, we reveal the transition to senescence to be controlled by chromatin state-specific transcription factor (TF) networks in younger and older donors independent of age.
These TF networks mediate widespread enhancer remodeling, repressing cell identity genes while upregulating inflammatory and secretory pathways. Inhibition or downregulation of AP1, KLF5, or RUNX2 modulates the transcriptional output and partially restores the blunted response to stimulation of senescent CD8 + T cells. Senescent CD8 + T cell gene signatures also predict responsiveness to chimeric antigen receptor (CAR)-T cell therapy in diffuse large B cell lymphomas.
Overall, our study defines the gene-regulatory mechanisms underlying human CD8 + T cell senescence, highlights TF network perturbation as a viable strategy to manipulate the senescence state, and identifies senescent CD8 + T cell gene signatures as prognostic tools for immunotherapy outcome.
论文信息
- 作者
- Turano PS、Akbulut E、Dewald HK、Vasilopoulos T、Fitzgerald-Bocarsly P、Herbig U、Martínez-Zamudio RI
- 第一作者单位
- Rutgers-New Jersey Medical School, Center for Cell Signaling, Department of Microbiology, Biochemistry and Molecular Genetics, 205 South Orange Avenue, Newark, NJ, USA.United States
- 通讯作者单位
- Rutgers-New Jersey Medical School, Center for Cell Signaling, Department of Microbiology, Biochemistry and Molecular Genetics, 205 South Orange Avenue, Newark, NJ, USA; Department of Pharmacology, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ, USA. Electronic address: ricardo.martinezzamudio@rutgers.edu.United States
- 期刊
- Cell reports2026 Jan 27
- 原文标识
- PubMed 41481417 · DOI 10.1016/j.celrep.2025.116795
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 →