在DNA损伤反应和ectonucleotidases之间的相互作用调节瘤对治疗的反应
John Stagg1, Encouse Golden2, Erik Wennerberg3
1Centre de Recherche du Centre Hospitalier de l'Université de Montréal, 900 St-Denis street, Montreal, QC H2X 0A9, Canada.
Science immunology
|July 7, 2023
概括
在瘤微环境中,ECTONUCLEOTIDASES将促炎信号转化为免疫抑制性腺,阻碍癌症疗法. 针对这些酶提供了新的免疫治疗和放射治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 由腺单酸盐 (AMP) 产生的细胞外腺,由ectonucleotidase CD73生成,可以减少组织炎症.
- 瘤微环境 (TME) 中的亲炎性核酸 (例如ATP,NAD+,cGAMP) 通过核酸酶 (CD39,CD38,ENPP1) 转化为AMP.
- 乙核核酸酶在TME内将免疫激活信号转化为免疫抑制信号,并阻止放射治疗等疗法诱导瘤排斥.
研究的目的:
- 审查腺在癌症中的免疫抑制作用.
- 阐明了ectonucleotidases在调节抗瘤免疫反应中的作用.
- 讨论针对腺生成和联合免疫疗法和放射治疗中的信号传导的治疗策略.
主要方法:
- 关于ectonucleotidases,腺和瘤微环境的研究的文献综述.
- 对ectonucleotidases影响免疫细胞功能和瘤进展的机制的分析.
- 讨论新出现的治疗目标和组合策略.
主要成果:
- 乙核酸酶通过产生腺在塑造免疫抑制性TME方面发挥着至关重要的作用.
- 通过其在免疫和癌细胞上的受体传递腺素信号,有助于免疫逃避.
- 释放亲炎性核酸的疗法可以通过ectonucleotidase活动来抵消.
结论:
- 向ectonucleotidases是增强抗瘤免疫力的有希望的策略.
- 结合疗法包括免疫疗法,放射疗法和ectonucleotidase 抑制剂可以克服治疗耐药性.
- 调节腺路径对于有效的癌症治疗至关重要.
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