增加的CCL2/CCR2轴通过增加M2巨细胞在MYC/BCL2双表达体DLBCL中促进瘤进展
Sehui Kim1,2, Hyein Jeong3,4, Hyun Kyung Ahn3,4
1Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Blood advances
|September 18, 2024
概括
骨髓细胞瘤基因 (MYC) 和B细胞淋巴瘤2 (BCL2) 双表达扩散大B细胞淋巴瘤 (DE-DLBCL) 途径涉及升高的C-C动机化学因配体2 (CCL2) 和C-C化学因受体2型 (CCR2),促进M2巨细胞的两极化和瘤的攻击性.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- MYC/BCL2双表达扩散型大B细胞淋巴瘤 (DE-DLBCL) 的发病原因尚未完全理解.
- MYC和BCL2是关键的瘤基因,与淋巴瘤的发展和进展有关.
- 了解瘤微环境在DE-DLBCL攻击性中的作用至关重要.
研究的目的:
- 调查MYC和BCL2对DE-DLBCL瘤攻击性的贡献.
- 阐明CCL2/CCR2轴在DE-DLBCL病原发生中的作用.
- 为了确定DE-DLBCL的潜在治疗点.
主要方法:
- 在DE-DLBCL和非DE-DLBCL瘤的全转录组测序.
- 使用公共数据集,患者组织,细胞系和小鼠淋巴瘤模型进行验证.
- 免疫组织化学评估免疫细胞透和蛋白质表达.
主要成果:
- 与非DE-DLBCL相比,DE-DLBCL显示显著增加了CCL2和CCR2mRNA水平.
- 增加的CCL2/CCR2与M2巨细胞透和减少的T细胞透相关.
- MYC/BCL2通过核因子 κB p65 调节了CCL2,促进了M2极化和瘤生长.
结论:
- CCL2/CCR2轴通过增强M2巨细胞极化,促进DE-DLBCL的攻击性.
- 增加的CCL2和CCR2表达与DLBCL患者的预后不佳有关.
- CCL2/CCR2轴代表了DE-DLBCL的潜在治疗目标.
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