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纤维细胞通过生物工程3D癌症结构中通过IL-6驱动免疫治疗中的差异反应

Srija Chakraborty, Marco Rodriguez, Aleksander Skardal

bioRxiv : the preprint server for biology

|July 16, 2025

概括

瘤微环境中的纤维细胞可以影响癌症治疗. 在激活的纤维细胞中阻断介质素-6 (IL-6) 途径可以恢复自然杀手 (NK) 细胞对瘤的免疫疗法的有效性.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
生物医学工程生物医学工程

背景情况:

瘤微环境的异质性使癌症治疗复杂化.
纤维细胞,关键的树突细胞,可以促进或抑制瘤.
了解纤维细胞-免疫细胞相互作用对于抗瘤免疫是至关重要的.

研究的目的:

研究纤维细胞在结直肠癌 (CRC) 化疗和免疫治疗中的作用.
阐明纤维细胞通过哪些机制影响瘤免疫细胞交叉交谈.
确定针对纤维细胞介导免疫抑制的治疗策略.

主要方法:

利用3D结肠直肠癌构造,这些构造来自细胞系在基于细胞外矩阵的水凝中.
评估了纤维细胞对化疗疗效的影响.
评估了纤维细胞对自然杀手细胞 (NK) 免疫疗法的影响,并确定了关键的细胞因子通路.

主要成果:

在3DCRC模型中,纤维细胞通常支持瘤细胞活力.
虽然纤维细胞影响了化疗的疗效,但效果不一致.
确定了介质素-6 (IL-6) 途径作为纤维细胞介导瘤细胞支持的机制.
在黑色素瘤瘤芯片模型中,通过阻断IL-6通路来证明NK细胞效应因子功能的恢复.

结论:

纤维细胞显著影响瘤细胞活力和免疫细胞相互作用.
向纤维细胞中的IL-6通路代表了增强NK细胞免疫疗法的潜在策略.
对纤维细胞-免疫细胞交叉的进一步研究可以揭示癌症治疗的新型治疗点.

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