AR+TREM2+巨细胞诱导的致病性免疫抑制促进前列腺癌的进展
Qiaohua Wang1, Yongjian Wu2, Yili Long1
1Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
Nature communications
|July 29, 2025
概括
与瘤相关的巨细胞 (TAMs) 中的雄激素受体 (AR) 和TREM2促进前列腺癌的生长. 向AR和TREM2可以克服治疗耐药性.
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:
- 雄激素受体 (AR) 驱动前列腺癌,但其在瘤相关巨细胞 (TAMs) 中的作用尚不清楚.
- TAMs在瘤微环境 (TME) 中至关重要,并影响癌症的进展和免疫逃避.
研究的目的:
- 为了研究AR和TREM2在前列腺癌中TAMs中的作用.
- 阐明AR和TREM2影响TME和瘤进展的机制.
- 探索针对前列腺癌中AR和TREM2的潜在治疗策略.
主要方法:
- 使用前列腺癌小鼠模型,对TREM2进行基因切除和药理性AR阻断.
- 研究了巨细胞中阿波利波蛋白E (APOE),TREM2和AR之间的相互作用.
- 在巨细胞中分析了AR,TREM2,APOE和免疫相关基因 (Il10,Tgfb1,Il23a,Ccl2) 的表达.
- 与患者预后相关的AR,TREM2和APOE表达.
主要成果:
- 共同表达AR和TREM2的巨体显示出免疫抑制和促进瘤的作用.
- 在小鼠模型中,遗传TREM2剥离和AR阻断显著降低了瘤进展.
- 在巨细胞上与TREM2结合的APOE增强了AR表达,这反过来又提高了免疫抑制基因的调节.
- 在人类前列腺癌患者中增加AR,TREM2和APOE表达与预后不佳相关.
结论:
- 在TAM中AR和TREM2代表了前列腺癌中瘤免疫逃避的新机制.
- 在TAM中准AR和TREM2提供了一种潜在的策略,以克服内分泌和免疫检查点治疗阻力.
- 这项研究为开发针对AR和TREM2的免疫调节剂用于前列腺癌治疗提供了理由.
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