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大 B 细胞淋巴瘤中 CD19 CAR-T 细胞治疗反应的预测因素:一项整合综述

英文原题:Predictors of response to CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a consolidated review.

查看英文原题

Predictors of response to CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a consolidated review.

PubMed 2025/09/03(内容时间) Curr Opin Oncol Q3 · IF 2.4(JCR 2025)

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中文摘要

综述目的:靶向CD19的CAR-T 细胞疗法改变了复发/难治性大B细胞淋巴瘤(LBCL)的治疗结局,但近半数接受治疗的患者仍会复发,毒性也较常见。亟需深入理解应答预测因素,以指导患者筛选、优化治疗并制定合理联合方案。近期发现:新证据显示,CAR-T 治疗应答受患者特异性因素、肿瘤内在因素及治疗相关因素共同影响。年龄、体能状态、炎症和微生物组组成等临床变量会影响疗效;肿瘤负荷、疾病分布、组织学亚型及基因组改变与耐药相关;桥接治疗、淋巴细胞清除方案和CAR-T 产品设计等治疗因素则影响细胞扩增、持久性和临床结局。免疫谱分析、放射组学及单细胞转录组学带来了更精细的认识和预测潜力。总结:CAR-T 应答预测因素涉及多种生物学和临床领域,且日益具有可操作性。将多模态生物标志物整合至常规流程,可实现个体化照护并改善结局。下一步需要前瞻性验证、实时监测和自适应试验设计,推动精准CAR-T 治疗。

展开英文摘要原文

PURPOSE OF REVIEW: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes for relapsed/refractory large B-cell lymphoma (LBCL), yet nearly half of treated patients relapse, and toxicities remain frequent. A deeper understanding of response predictors is urgently needed to guide patient selection, treatment optimization, and development of rational combination strategies. RECENT FINDINGS: Emerging data reveal that response to CAR-T therapy is shaped by patient-specific, tumor-intrinsic, and treatment-related factors. Clinical variables such as age, performance status, inflammation, and microbiome composition influence efficacy.

Tumor burden, disease distribution, histologic subtype, and genomic alterations correlate with resistance. Treatment factors, including bridging strategies, lymphodepletion regimen, and CAR-T product design, affect expansion, persistence, and clinical outcomes. Novel insights from immune profiling, radiomics, and single-cell transcriptomics offer further granularity and predictive potential.

SUMMARY: Predictors of CAR-T response span diverse biological and clinical domains and are increasingly actionable. Integrating multimodal biomarkers into routine workflows can personalize care and improve outcomes. Prospective validation, real-time monitoring, and adaptive trial designs are essential next steps toward precision CAR-T therapy.

论文信息

作者
Ben Valid O、Shouval R
第一作者单位
The Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, affiliated with Faculty of Medicine, Tel Aviv University, Israel.Israel
通讯作者单位
Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center.
文献类型
综述
期刊
Current opinion in oncology2025 Nov 1
原文标识
PubMed 41029962 · DOI 10.1097/CCO.0000000000001188