3D瘤微环境相互作用揭示了AP-1复杂调节和在慢性淋巴细胞白血病中骨髓 stromal 细胞的接触介导重编程
Jana Lindacher1,2, Anne Hartebrodt3, Janin Dingfelder1,2
1Department of Internal Medicine 5, Hematology and Oncology Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) Erlangen Germany.
HemaSphere
|August 14, 2025
概括
慢性淋巴细胞白血病细胞重新编程其瘤微环境以抵抗药物. 准AP-1和树皮细胞可能会改善慢性淋巴细胞白血病 (CLL) 治疗.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 慢性淋巴细胞白血病 (CLL) 细胞操纵瘤微环境 (TME),以增强耐药性和疾病进展.
- 瘤细胞存活受到与非恶性细胞的相互作用的严重影响,特别是骨髓衍生性树皮细胞 (BMSCs).
研究的目的:
- 在3D模型中研究CLL B细胞,T细胞和BMSC之间的直接细胞-细胞相互作用.
- 了解CLL细胞如何利用TME发展治疗耐药性.
主要方法:
- 利用一个三维 (3D) 共同培养系统来模拟体内条件.
- 分析了复杂的脚手架状结构中的细胞-细胞相互作用和分子变化.
主要成果:
- 在3D结构的核心区域的CLL细胞上调了AP-1,赋予了治疗耐药性.
- 在核心区域观察到调控性T细胞 (Tregs) 和卵泡辅助性T细胞 (TfH) 的丰度增加.
- 细胞诱导了BMSC重编程,形成了具有癌症相关纤维细胞样特征的独特人群.
结论:
- 细胞利用TME,特别是BMSC来促进生存和耐药性.
- 在CLL细胞中AP-1的升级是治疗耐药性的关键机制.
- 准AP-1和体区为CLL提供了潜在的治疗策略.
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