向ENO1重新编程巨细胞两极分化以触发抗瘤免疫力,并改善放射治疗的治疗效果
Yu-Sen Lin1, Hsin-Yu Chang2,3, Wei-Ze Hong3
1Department of Chest Surgery, China Medical University Hospital, Taichung, Taiwan.
Cell death & disease
|February 2, 2026
概括
用抗体准表面Enolase 1 (ENO1) 通过重编程瘤微环境来减少瘤生长和转移. 这种方法可以提高结直肠癌和三阴性乳腺癌的放射疗效.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 乙醇酶1 (ENO1) 是一种糖解酶,通过各种功能与瘤进展有关.
- 通过ENO1促进瘤进展的确切机制仍未完全阐明.
- 了解ENO1的作用对于开发新型癌症疗法至关重要.
研究的目的:
- 为了研究ENO1介导的瘤进展的机制.
- 探索针对癌症治疗的表面ENO1的潜力.
- 评估向ENO1对瘤微环境和对放射治疗的反应的影响.
主要方法:
- 研究了TGFβ1/Smad3信号通路在ENO1修饰中的作用.
- 使用蛋白质氨酸甲基转移酶5 (PRMT5) 来研究ENO1二甲基化.
- 使用一个人性化抗体 (HuL001) 准表面ENO1.1.
- 评估了对糖解,乳酸分泌,巨细胞两极分化和瘤生长的影响.
- 评估了与HuL001.1.结合放射治疗的治疗反应.
主要成果:
- TGFβ1/Smad3信号诱导ENO1通过PRMT5进行对称二甲基化,导致其转移到细胞膜.
- 表面ENO1与MCT4相互作用,促进乳酸分泌,M2巨细胞的招募,以及免疫抑制瘤微环境 (TME).
- 用HuL001准表面ENO1抑制了瘤生长,转移,并重新编程了TME.
- 使用HuL001和放射治疗的联合治疗通过增加M1巨细胞和CD8+T细胞来增强抗瘤免疫力.
结论:
- 准表面ENO1有效地重塑了瘤的微环境.
- 针对ENO1的抗体介导增强了在免疫性较差的结直肠癌和三阴性乳腺癌中放射治疗的疗效.
- 表面ENO1代表了改善癌症治疗结果的有希望的治疗标.
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