分泌的PTEN与巨细胞结合PLXDC2,驱动抗瘤免疫和瘤抑制
Cheng Zhang1, Hong-Ming Ma2, Shuai Wu3
1Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China; School of Basic Medicine and Life Science, Hainan Academy of Medical Sciences, Hainan Medical University, Haikou, Hainan 571199, China.
酸酶和张素同类素 (PTEN) 的损失可以被分泌出来,作为一种细胞因子来增强抗瘤免疫力. 细胞外PTEN蛋白疗法增强免疫细胞活性,抑制瘤生长,提供新的癌症治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 酸酶和张素同源体 (PTEN) 的损失与免疫抑制性瘤微环境有关.
- 通过PTEN影响瘤免疫力的机制尚未完全理解.
研究的目的:
- 研究分泌的PTEN在调节瘤微环境和抗瘤免疫力中的作用.
- 探索细胞外PTEN在癌症免疫治疗中的治疗潜力.
主要方法:
- 通过TMED10通路研究PTEN分泌.
- 在小鼠模型中内注射PTEN蛋白.
- 分析了巨细胞表型切换和免疫细胞激活 (CD8+ T细胞,NK细胞).
- 评估了PTEN治疗与抗PD-1疗法结合的疗效.
主要成果:
- 通过TMED10途径分泌PTEN;抑制分泌促进免疫抑制.
- 细胞外PTEN与巨细胞结合PLXDC2,从而激活JAK2-STAT1信号传递.
- 这将TAM转换为炎症表型,增强CD8+ T和NK细胞活性.
- 治疗PTEN抑制了瘤生长,提高了抗PD-1的疗效,并逆转了免疫抑制TAM表型.
结论:
- PTEN作为一种类似于细胞因子的分子,可以激活抗瘤免疫力.
- 细胞外PTEN的使用显示出癌症免疫疗法的显著治疗潜力.
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