通过调节免疫抑制性巨细胞极化,AXL促进炎症性乳腺癌的进展
Lan T H Phi1,2, Yating Cheng1, Yohei Funakoshi1
1Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Breast cancer research : BCR
|May 6, 2025
概括
向瘤相关巨细胞 (TAMs) 中的AXL信号,通过减少M2巨细胞极化和免疫抑制因素来抑制炎症性乳腺癌 (IBC) 的生长. 这突出了AXL作为侵略性IBC的潜在治疗点.
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:
- 与瘤相关的巨细胞 (TAMs) 驱动着炎症性乳腺癌 (IBC) 的进展.
- AXL受体氨酸激酶在IBC中高度表达,但其在TAMs中的作用尚不清楚.
研究的目的:
- 研究AXL信号在IBC瘤微环境中的TAMs中的作用.
- 在IBC中评估AXL抑制的治疗潜力.
主要方法:
- 使用IBC和三阴性乳腺癌的小鼠模型来评估AXL抑制剂TP-0903的影响.
- 用AXL淘汰THP-1单细胞进行了体外研究.
- 使用了流细胞计,免疫组织化学,RNA测序和CIBERSORT解卷.
主要成果:
- 抑制AXL降低了IBC瘤生长和M2巨细胞群.
- 通过STAT6.6,AXL信号促进M2极化和免疫抑制化学因子 (CCL20,CCL26,epiregulin) 的分泌.
- 高AXL表达与免疫抑制细胞相关,与IBC患者组织中的免疫活性细胞相反.
结论:
- 通过AXL信号驱动IBC生长,促进M2巨细胞的两极分化,并通过STAT6.6创建免疫抑制瘤微环境.
- 向AXL代表了IBC的一个有前途的治疗策略,需要进行临床研究.
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