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重组 TRAIL 在瘤免疫微环境中的剂量相关的免疫调节效应

Xupu Wang¹, Lizheng Wang^1,2, Wenmo Liu¹

¹National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.

Journal of experimental & clinical cancer research : CR

|August 22, 2023

概括

与重组瘤亡因子 (TNF) 相关的诱导亡的配体 (TRAIL) 对瘤微环境具有剂量依赖的影响. 最佳剂量激活抗瘤免疫力,而较高剂量促进瘤生长,这表明定制的 TRAIL 策略对于癌症治疗至关重要.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
药物开发药物开发

背景情况:

与重组瘤亡因子 (TNF) 相关的诱导亡的配体 (TRAIL) 影响癌症免疫微环境,但其机制尚不清楚.
了解TRAIL的免疫调节作用对于开发新型癌症疗法至关重要.

研究的目的:

在瘤微环境 (TME) 中研究重组 TRAIL 的免疫调节效应和机制.
探索结合TRAIL与其他药物的潜在治疗策略.

主要方法:

具有瘤的免疫能力较强的小鼠被用不同剂量的重组 TRAIL 治疗.
使用流细胞计和单细胞测序进行了免疫学检测和机械学调查.
用一个人性化的免疫系统小鼠模型来验证与人类 TRAIL 的发现.

主要成果:

再组合溶解小鼠 TRAIL (smTRAIL) 显示了剂量依赖的免疫调节效应.
最佳smTRAIL剂量 (2mg/kg) 激活了先天性免疫细胞和CD8+ T细胞.
较高的smTRAIL剂量 (8 mg/kg) 促进了促进瘤的微环境,包括M2样巨细胞和IL-10的产生,抑制NK和CD8+T细胞.
再组合可溶性人类TRAIL (shTRAIL) 和trabectedin的联合管理重塑了TME,增强了抗瘤免疫力,并在人性化的模型中改善了治疗效果.

结论:

再组合 TRAIL 在TME中起着重要的免疫调节作用.
量身定制的 TRAIL 管理和组合疗法在临床癌症治疗中显示出有前途.

关键词:

免疫调节免疫调节轨道的轨道是一个轨道.与瘤相关的巨细胞.

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