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T细胞特征对血液系统恶性肿瘤中CAR-T细胞疗法的影响。

Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies.

作者信息

Tao Zhongfei, Chyra Zuzana, Kotulová Jana, Celichowski Piotr, Mihályová Jana, Charvátová Sandra, Hájek Roman

机构信息

Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.

Department of Haematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.

出版信息

Blood Cancer J. 2024 Dec 3;14(1):213. doi: 10.1038/s41408-024-01193-6.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigms for hematological malignancies. However, more than half of these patients cannot achieve sustainable tumor control, partially due to the inadequate potency of CAR-T cells in eradicating tumor cells. T cells are crucial components of the anti-tumor immune response, and multiple intrinsic T-cell features significantly influence the outcomes of CAR-T cell therapy. Herein, we review progressing research on T-cell characteristics that impact the effectiveness of CAR-T cells, including T-cell exhaustion, memory subsets, senescence, regulatory T-cells, the CD4 to CD8 T-cell ratio, metabolism, and the T-cell receptor repertoire. With comprehensive insight into the biological processes underlying successful CAR-T cell therapy, we will further refine the applications of these novel therapeutic modalities, and enhance their efficacy and safety for patients.

摘要

嵌合抗原受体(CAR)T细胞疗法彻底改变了血液系统恶性肿瘤的治疗模式。然而,超过半数的此类患者无法实现持久的肿瘤控制,部分原因是CAR-T细胞在根除肿瘤细胞方面的效力不足。T细胞是抗肿瘤免疫反应的关键组成部分,多种T细胞内在特性显著影响CAR-T细胞疗法的疗效。在此,我们综述了关于影响CAR-T细胞有效性的T细胞特性的研究进展,包括T细胞耗竭、记忆亚群、衰老、调节性T细胞、CD4与CD8 T细胞比率、代谢以及T细胞受体库。通过全面深入了解成功的CAR-T细胞疗法背后的生物学过程,我们将进一步优化这些新型治疗方法的应用,并提高其对患者的疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45ac/11615218/1a5d53d9c161/41408_2024_1193_Fig1_HTML.jpg

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