瘤细胞诱导神经DKK1表达,促进MDSC透和随后的T细胞抑制
Ruoyan Liu1, Xiaotian Shi2, Shuangshuang Qian2
1Department of Gynaecological Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China; Tianjin Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin 300060, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Cellular signalling
|December 22, 2024
概括
瘤细胞可以增加神经DKK1的表达,通过髓质衍生抑制细胞 (MDSC) 促进免疫抑制. 通过向这种途径,可以通过减少MDSC和增强T细胞活性来提供新的癌症疗法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
背景情况:
- 神经是瘤微环境的组成部分,但它们与瘤的分子相互作用尚不清楚.
- 散布的瘤神经相互作用是头部和部状细胞癌 (HNSCC) 和胰腺导管腺癌 (PDAC) 的特征.
研究的目的:
- 研究瘤神经相互作用的分子机制及其对瘤微环境的影响.
- 为了测试瘤诱导神经DKK1表达的假设,这促进了骨髓衍生抑制细胞 (MDSC) 透和免疫抑制.
主要方法:
- 对DKK1表达和患者预后的癌症基因组图谱 (TCGA) 数据的分析.
- 在实验室中与瘤细胞共同培养三腺.
- 在小鼠的体内正位素瘤模型中,DKK1中和或有条件的神经元DKK1删除.
- 多重免疫组织化学和血DKK1水平测量.
主要成果:
- 在HNSCC和PDAC中,DKK1表达与预后不佳和MDSC透相关.
- 瘤细胞诱导DKK1在神经细胞中的表达在体外和体内.
- 在体内DKK1中和降低了MDSC水平和T细胞抑制.
- 神经元DKK1缺失导致MDSC透和免疫抑制受损.
结论:
- 瘤细胞通过诱导神经中DKK1的表达来操纵免疫微环境.
- 这种新的瘤神经免疫轴突出了DKK1作为增强抗瘤免疫力的潜在治疗点.
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