来自瘤的红蛋白作为癌症免疫力的免疫抑制开关
David Kung-Chun Chiu1, Xiangyue Zhang1, Bowie Yik-Ling Cheng2
1Department of Pathology, Stanford University, Stanford, CA, USA.
概括
来自癌细胞的红素 (EPO) 通过EPOR在巨细胞上发出信号,从而产生免疫抑制性瘤微环境 (TME). 阻断这个EPO/EPOR轴促进炎症TME和瘤回归,增强免疫疗法.
科学领域:
- 免疫学
- 癌症学
- 癌症研究
背景情况:
- 有效的癌症免疫疗法依赖于对瘤的强有力的免疫反应.
- 许多癌症会发展出逃避免疫系统检测和破坏的机制.
- 了解免疫规避对于改善癌症治疗结果至关重要.
研究的目的:
- 研究瘤逃避免疫监测的分子机制.
- 确定决定瘤微环境 (TME) 免疫型的关键因素.
- 探索针对肝细胞癌 (HCC) 免疫规避的治疗策略.
主要方法:
- 使用自发性小鼠肝细胞癌 (HCC) 模型.
- 炎症 (富含T细胞) 和非炎症 (缺乏T细胞) 的瘤微环境的比较.
- 研究了红质素 (EPO) 和其受体 (EPOR) 对瘤相关巨细胞 (TAM) 的作用.
主要成果:
- 瘤分泌的EPO被确定为瘤免疫型的关键决定因素.
- 在TAM上通过EPOR发出信号,诱发了免疫抑制的,非炎症的TME.
- 通过EPO/EPOR信号的NRF2介导的血耗尽使TAMs具有免疫调节作用.
- 瘤衍生的EPO或TAMEPOR的抑制导致了炎症TME和瘤回归.
结论:
- 在EPO/EPOR轴作为一个免疫抑制开关,阻碍抗瘤免疫力.
- 针对EPO/EPOR途径可以将非炎症的TME转化为炎症的TME,促进瘤回归.
- 这一途径是增强癌症免疫疗法的潜在治疗点.
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