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.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
YTHDF2 促进 B 细胞恶性肿瘤中的 ATP 合成与免疫逃逸
英文原题：YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.
查看英文原题
YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
CAR-T 细胞免疫治疗后，B细胞恶性肿瘤患者长期持久缓解仍不理想，常因抗原逃逸而复发。恶性B细胞转化和致癌性生长依赖高效ATP合成，但其机制尚不明确。本研究报告，YTHDF2促进B细胞恶性肿瘤能量供应及抗原逃逸，且单独过表达YTHDF2就足以引起B细胞转化和肿瘤发生。从机制上看，YTHDF2兼具双重RNA识别功能：作为5-甲基胞嘧啶（m5C）识别蛋白，它通过募集PABPC1稳定mRNA，从而提高相应表达及ATP合成；同时，作为N6-甲基腺苷（m6A）识别蛋白，它可使其他mRNA不稳定，从而促进免疫逃逸。使用小分子靶向YTHDF2可抑制侵袭性B细胞恶性肿瘤，并使肿瘤对CAR-T 细胞疗法更敏感。
展开英文摘要原文
Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear.
Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.
Mechanistically, YTHDF2 functions as a dual reader where it stabilizes mRNAs as a 5-methylcytosine (m 5 C) reader via recruiting PABPC1, thereby enhancing their expression and ATP synthesis. Concomitantly, YTHDF2 also promotes immune evasion by destabilizing other mRNAs as an N 6 -methyladenosine (m 6 A) reader. Small-molecule-mediated targeting of YTHDF2 suppresses aggressive B cell malignancies and sensitizes them to CAR-T cell therapy.
论文信息
- 作者
- Chen Z、Zeng C、Yang L、Che Y、Chen M、Sau L、Wang B、Zhou K
- 第一作者单位
- Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; Center for RNA Biology and Therapeutics, City of Hope Beckman Research Institute, Duarte, CA 91010, USA. Electronic address: zhenhchen@coh.org.United States
- 通讯作者单位
- Department of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; Center for RNA Biology and Therapeutics, City of Hope Beckman Research Institute, Duarte, CA 91010, USA. Electronic address: jianchen@coh.org.United States
- 期刊
- Cell2025 Jan 23
- 原文标识
- PubMed 39694037 · DOI 10.1016/j.cell.2024.11.007
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →