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诱导缺氧的冷凝揭示了缺氧瘤微环境中的关键癌症免疫细胞相互作用

Thibault Colombani¹, Zachary J Rogers¹, Khushbu Bhatt²

¹Department of Chemical Engineering, Northeastern University, Boston, MA 02115, United States.

Bioactive materials

|August 21, 2023

概括

新的低氧诱导型冷凝 (HIC) 有效地模拟瘤微环境. 这些先进的癌症模型揭示了缺氧如何影响免疫细胞,为开发更好的癌症疗法提供了见解.

科学领域:

生物医学工程生物医学工程
癌症生物学癌症生物学
免疫学免疫学免疫学

背景情况:

缺氧显著影响瘤免疫微环境,但目前的癌症模型有局限性.
现有的模型往往缺乏可重现性,充足的生物物理线索和适当的氧气控制,导致瘤反应不准确.

研究的目的:

为了设计先进的3D微组织,准确地模仿瘤相关的缺氧和细胞外基质.
为了研究缺氧对免疫细胞透和功能在一个更生理相关的瘤模型中的影响.

主要方法:

开发了使用氨酸 (HA) 制造3D微组织的低氧诱导冷凝 (HICs).
将瘤细胞纳入HIC,以诱导局部,持续的缺氧.
分析了基因表达,代谢变化,化疗耐药性和免疫细胞反应 (树突细胞和CD8+ T细胞).

主要成果:

HICs成功诱导长期缺氧,改变基因表达,促进代谢适应和化疗耐药性.
在HICs中的缺氧条件导致树突细胞 (DC) 抑制,影响血细胞 (pDC) 和常规 (cDC) 子集.
基于HIC的黑色素瘤模型展示了CD8+T细胞抑制,其特征是减少的促炎性细胞因子和细胞毒性能力.

结论:

HIC 作为一种强大的工具,用于模拟类似固体的瘤微环境,并在低氧条件下研究癌症与免疫相互作用.
这些发现加深了对在低氧环境中免疫逃避的理解.
HIC技术具有促进癌症研究和治疗开发的潜力.

关键词:

癌症癌症癌症癌症冰冷凝是一种冷凝.药物耐药性药物耐药性药物耐药性氧气过低是因为缺氧.免疫抑制是一种免疫抑制.

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