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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Clonal Hematopoiesis and CAR T Cell Therapy: From Biological Crosstalk to Clinical Implications.
Clonal Hematopoiesis and CAR T Cell Therapy: From Biological Crosstalk to Clinical Implications.
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克隆性造血(CH)日益被认为是衰老和癌症中的重要生物学现象,其特征为携带髓系肿瘤相关基因体细胞突变的造血干细胞和祖细胞扩增。CH与多种炎症性疾病及血液系统恶性肿瘤密切相关,但其在塑造癌症免疫治疗应答中的作用,尤其是对嵌合抗原受体(CAR)T细胞疗法的影响,直到近期才开始受到关注。本综述探讨CH与CAR-T 疗法的相互作用,重点讨论接受治疗人群中的CH患病率、治疗后克隆动态、炎症毒性及治疗相关髓系肿瘤风险。我们还讨论特定CH突变对造血、免疫细胞功能及CAR-T 细胞持久性的不同影响。理解CAR-T 治疗背景下CH的功能意义,有望优化患者选择、调整毒性管理并推动个体化免疫治疗策略开发。
Clonal hematopoiesis (CH) is increasingly recognized as a significant biological phenomenon in aging and cancer, marked by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations in genes associated with myeloid neoplasms.
While CH is strongly linked to a spectrum of inflammatory diseases and hematologic malignancies, its role in shaping responses to cancer immunotherapy-especially chimeric antigen receptor (CAR) T cell therapy-has only recently begun to emerge. This review explores the interplay between CH and CAR T cell therapy, highlighting CH prevalence in treated populations, post-therapy clonal dynamics, inflammatory toxicities, and risk of therapy-related myeloid neoplasms.
We also discuss the differential effects of specific CH mutations on hematopoiesis, immune cell function, and CAR T cell persistence. Understanding the functional implications of CH in the context of CAR T cell therapy holds the potential to refine patient selection, tailor toxicity management, and develop personalized immunotherapeutic approaches.
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