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
METTL16 调控的 TCF-1 m6A 高甲基化促进急性髓系白血病
英文原题：m6A hypermethylation of TCF-1 regulated by METTL16 promotes acute myeloid leukemia.
查看英文原题
m6A hypermethylation of TCF-1 regulated by METTL16 promotes acute myeloid leukemia.
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研究概要
METTL16 缺失可促进 CAR-T 细胞的持久性与记忆形成，在急性髓系白血病中。
中文摘要
背景
甲基转移酶16（METTL16）在多种癌症（包括白血病）中发挥致癌作用，但其在急性髓系白血病（AML）中的作用报道有限。本研究旨在探讨METTL16在AML中的潜在作用。
方法
采用RT-qPCR检测AML患者和健康对照中的METTL16表达；以m6A检测分析m6A水平；采用甲基化RNA免疫沉淀（MeRIP）检测AML细胞T细胞因子1（TCF-1）转录本的m6A高甲基化；通过流式细胞术分析嵌合抗原受体（CAR）T细胞功能。
结果
AML患者中METTL16上调，高表达与预后不良相关。功能上，METTL16缺失可促进CAR-T 细胞持续存在和肿瘤杀伤能力，并促进CAR-T 细胞分化为TCF-1前体耗竭T细胞（TPEX）。METTL16介导TCF-1的m6A修饰，并抑制其mRNA表达和稳定性。TCF-1缺失会促进T细胞耗竭并抑制其自我更新能力。
结论
总之，METTL16缺失可促进AML中CAR-T 细胞持续存在及记忆形成。因此，靶向METTL16可能增强AML抗肿瘤免疫。
展开英文摘要原文
BACKGROUND
Methyltransferase 16 (METTL16) functions as an oncogene in various cancer, including leukemia. However, the role of METTL16 in acute myeloid leukemia (AML) is scarcely reported. The present study aimed to investigate the potential of METTL16 in AML.
METHODS
RT-qPCR was used to METTL16 expression in AML patients and healthy control. m6A levels was determined using m6A assay. Methylated RNA immunoprecipitation (MeRIP) assay applied for determining m6A hypermethylation of T cell factor 1 (TCF-1) transcripts in AML cells. Chimeric antigen receptor (CAR)-T-cell functions were analyzed using flow cytometry.
RESULTS
METTL16 is upregulated in AML patients. High levels of METTL16 were associated with poor prognosis of AML patients. Functionally, METTL16 deficiency promoted the persistence and tumor-killing ability of CAR-T cells. Moreover, METTL16 deficiency promoted the differentiation of CAR-T cells into TCF-1 precursor exhausted T cells (T PEX ). METTL16 mediated the m6A modification of TCF-1 and inhibited its mRNA expression and stability. TCF-1 deficiency promoted the exhaustion and inhibited the self-renewal ability of T cells.
CONCLUSION
Collectively, METTL16 deficiency promoted the persistence of CAR-T cells and memory formation in AML. Therefore, targeting METTL16 may stimulate the anti-tumor immunity in AML.
论文信息
- 作者
- Li J、Kang H
- 第一作者单位
- Department of Hematology, Shanxi Maternal and Child Health Hospital, No. 13, Xinmin North Street, Taiyuan, 030000, China.China
- 通讯作者单位
- Department of Hematology, Shanxi Maternal and Child Health Hospital, No. 13, Xinmin North Street, Taiyuan, 030000, China. kang_hui006@163.com.China
- 期刊
- Clinical and experimental medicine2025 Apr 29
- 原文标识
- PubMed 40299085 · DOI 10.1007/s10238-025-01669-0
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