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瘤细胞的可追踪的in vivo重编程,使其成为1型常规的树突细胞样细胞

Ervin Ascic¹, Gaia Fontanari¹, Maria Thrasyvoulou¹

¹Molecular Medicine and Gene Therapy, Science for Life Laboratory, Lund Stem Cell Centre, Lund University; Wallenberg Centre for Molecular Medicine, Lund University.

Journal of visualized experiments : JoVE

|August 18, 2025

概括

研究人员开发了一种新的癌症免疫疗法,通过将瘤细胞重新编程成瘤微环境中的树突细胞 (cDC1类细胞). 这种方法通过促进细胞毒性T细胞对固体瘤的反应来增强抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
生物技术是生物技术.

背景情况:

1型常规树突细胞 (cDC1s) 对于抗癌T细胞反应至关重要.
目前用于产生cDC1s用于免疫治疗的方法受到低产量,功能可变性和瘤微环境 (TME) 抑制的限制.

研究的目的:

开发一种新的体内重编程策略,在TME中将癌细胞转化为cDC1类细胞.
建立一个可处理的协议,用于产生免疫性cDC1-like细胞,用于增强癌症免疫疗法.

主要方法:

在癌细胞中过度表达核心cDC1基因网络 (PU.1,IRF8,BATF3 - PIB).
皮下植入PIB转化和父癌细胞混合物的皮下植入.
监测细胞表面标记物 (CD45,MHCII类) 作为重新编程效率的读数.

主要成果:

在YUMM1.7黑色素瘤模型中的体内重编程显示出比体内方法更快的动力学和更高的效率.
重编程的cDC1-样细胞在9天内诱导了快速的TME重塑,免疫细胞透和三级淋巴体结构的形成.
重编程的细胞在瘤中持续至少9天,显示出持续的免疫性潜力.

结论:

在体内描述的cDC1重编程协议提供了一种强大的方法,可以将"免疫冷"瘤转化为"免疫热"瘤.
这种方法为研究cDC1介导的抗瘤免疫力和探索组合免疫疗法提供了一个平台.

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