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在瘤微环境条件下的巨细胞中使用XAV939纳米粒子准Wnt/β-catenin信号传递促进免疫性

Chetan Pundkar¹, Ferrin Antony¹, Xuejia Kang^2,3

¹Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.

|June 14, 2023

概括

抑制瘤相关巨细胞中的Wnt/β-catenin信号传递增强了它们刺激抗瘤T细胞反应的能力. 这种使用XAV939纳米粒子的方法可以通过促进瘤微环境中的免疫细胞活性来改善癌症免疫疗法.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
药理学药理学是指药理学的学科.

背景情况:

在瘤微环境 (TME) 中异常的Wnt/β-catenin信号驱动癌症的进展和免疫逃避.
虽然树突细胞中的Wnt/β-catenin激活会损害抗瘤免疫力,但其在瘤相关巨细胞 (TAMs) 中的作用尚不清楚.
TAMs作为抗原呈现细胞 (APC) 起作用,并影响TME内的抗瘤免疫反应.

研究的目的:

调查TME条件下的巨细胞中抑制β-catenin是否会提高它们的免疫性.
评估针对TAM中β-catenin的治疗潜力,以促进抗瘤免疫力.

主要方法:

使用XAV939 (XAV-Np) 的纳米粒子配方,一种坦基拉酶抑制剂,以促进β-catenin的降解.
进行了体外巨细胞共同培养测定与黑色素瘤细胞 (MC) 或黑色素瘤细胞超级生物 (MCS).
评估了巨细胞表面标记表达 (CD80,CD86,PD-L1,CD206),细胞因子产生 (IL-6,TNF-α,IL-10) 和T细胞增殖的变化.

主要成果:

在MC/MCS条件下的巨细胞上,XAV-Np治疗提高了CD80/CD86的调节,并抑制了PD-L1/CD206.
接受XAV-Np治疗的巨体显示IL-6和TNF-α的产生增加,IL-10的减少.
与XAV-Np处理的巨细胞共同培养显著增强了CD8+ T细胞的增殖.

结论:

针对性地抑制TAM中的β-catenin促进了巨细胞的免疫性.
这一策略增强了TAMs刺激抗瘤T细胞反应的能力.
在TAM中抑制β-catenin代表了增强抗瘤免疫力的有希望的治疗途径.

关键词:

抗瘤免疫力抗瘤免疫力免疫耐受性的免疫耐受性免疫性免疫性免疫性纳米颗粒是如何形成的瘤微环境是一个微环境.与瘤相关的巨细胞.他们不想做.在XAV93939中使用.这是一种β-catenin.

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