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克服高危 DLBCL 中 CAR-T 瓶颈:分子分型增效策略

英文原题:Overcoming CAR-T bottlenecks in high-risk DLBCL: a molecular subtyping enhancement strategy.

查看英文原题

Overcoming CAR-T bottlenecks in high-risk DLBCL: a molecular subtyping enhancement strategy.

PubMed 2025/11/17(内容时间) Cancer Cell Int Q1 · IF 7(JCR 2025)

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中文摘要

弥漫性大B细胞淋巴瘤(DLBCL)是非霍奇金淋巴瘤中最常见的亚型,具有显著的分子异质性,导致患者治疗反应各异。尽管CAR-T 细胞疗法(CAR-T)在复发/难治性(R/R)DLBCL中取得了显著进展,尤其是在对标准治疗耐药的患者中,但CAR-T 疗法对高危亚型(如双打击/三打击淋巴瘤(DHL/THL)和TP53突变)的疗效仍不一致。本文聚焦于DLBCL的分子分型及其在CAR-T 疗法中的应用。通过分析代谢应激、免疫逃逸和表观遗传调控等因素,本研究揭示了这些机制如何影响CAR-T 细胞的功能和疗效。此外,本文还探讨了通过分子分型、代谢调节、表观遗传干预和多靶点联合治疗来克服高危亚型治疗挑战的策略。本文还展望了CAR-T 细胞工程和免疫逃逸机制的未来研究方向。本研究为个性化治疗提供了新的理论框架,并为高危DLBCL患者的临床治疗策略提供了有价值的见解。

展开英文摘要原文

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and exhibits significant molecular heterogeneity, leading to varied treatment responses among patients. Although Chimeric Antigen Receptor T-cell therapy (CAR-T) has made remarkable progress in relapsed/refractory (R/R) DLBCL, particularly in patients resistant to standard treatments, the therapeutic efficacy of CAR-T therapy remains inconsistent for high-risk subtypes, such as double-hit/triple-hit lymphoma (DHL/THL) and TP53 mutations.

This paper focuses on the molecular subtyping of DLBCL and its application in CAR-T therapy. By analyzing factors such as metabolic stress, immune evasion, and epigenetic regulation, this study reveals how these mechanisms influence the function and efficacy of CAR-T cells.

Furthermore, it discusses strategies for overcoming treatment challenges in high-risk subtypes through molecular profiling, metabolic modulation, epigenetic interventions, and multi-target combination therapies. The paper also explores future research directions in CAR-T cell engineering and immune evasion mechanisms. This research provides a novel theoretical framework for personalized treatment and offers valuable insights for clinical treatment strategies for high-risk DLBCL patients.

论文信息

作者
Zheng R、Zhu X、Xiao Y
第一作者单位
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.China
通讯作者单位
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. yixiao@tjh.tjmu.edu.cn.China
文献类型
综述
期刊
Cancer cell international2025 Nov 17
原文标识
PubMed 41254710 · DOI 10.1186/s12935-025-04046-9