瘤衍生的外体ENTPD2通过ATP-腺酸代谢重编程损害结肠癌中CD8+ T细胞功能
Mengchen Shi1,2,3, Linsen Ye4, Lu Zhao1,3
1Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
Cell communication and signaling : CCS
|May 16, 2024
概括
结肠癌细胞释放出外体ENTPD2,它通过改变ATP-腺酸代谢来抑制免疫微环境. 这一发现揭示了外体酶衍生的酶.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 细胞外ATP-AMP-腺代谢影响瘤免疫反应.
- 乙核酸三酸二酸酶1 (ENTPD1/CD39) 主要催化ATP转化为AMP.
- 瘤细胞衍生ATPases在结肠癌中的作用尚不清楚.
研究的目的:
- 研究结肠癌细胞衍生ATPases在结肠癌发育和进展中的作用.
主要方法:
- 对结肠癌中的ATPase表达的生物信息和组织微阵列分析.
- 在体外测试 (ATP水解,CCK8,殖民地形成) 来评估ENTPD2的影响.
- 流细胞计,RNA-seq,免疫电子显微镜,西部涂抹和免疫光检测,以评估ENTPD2的功能和局部化.
主要成果:
- ENTPD2,而不是CD39,在结肠癌细胞中表达高,与预后不佳有关.
- 在癌细胞中过度表达的ENTPD2通过抑制CD8+T细胞功能来促进瘤的进展.
- 外体ENTPD2降低了细胞外ATP,抑制了P2X7R-NFATc1信号传递,并促进了腺-A2AR通路活性.
- 血清外体ENTPD2水平与晚期TNM阶段,瘤入侵相关,并且与CD8+T细胞透负相关.
结论:
- 来自结肠癌细胞的外体ENTPD2通过ATP-腺酸代谢创造了一个免疫抑制的微环境.
- 外体源的水解酶在塑造瘤免疫微环境方面至关重要.
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