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由瘤治疗场 (TTFields) 诱导的亲炎性巨细胞表现型曲

Tal Kan¹, Yiftah Barsheshet¹, Tharwat Haj Khalil¹

¹Novocure Ltd., Haifa 3190500, Israel.

International journal of molecular sciences

|December 30, 2025

概括

瘤治疗场 (TTFields) 直接将免疫抑制的M2类巨细胞重编程为一种促炎的M1类状态. 这种由TTFields进行的免疫调节可以在瘤微环境 (TME) 中增强抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物物理学的生物物理.

背景情况:

与瘤相关的巨细胞 (TAMs) 经常表现出免疫抑制的M2表型,促进瘤生长.
将TAM重编程为促炎M1状态是一种有前途的癌症治疗策略.
瘤治疗场 (TTFields) 是FDA批准的电场疗法,具有已知的抗真菌作用.

研究的目的:

调查TTFields对巨细胞激活和功能的直接影响.
为了确定TTFields是否可以将免疫抑制TAM重编程到一种抗瘤原始的表型.

主要方法:

来自小鼠骨髓的巨细胞 (BMDMs) 偏向M1或M2表型,并暴露于TTFields.
分析了巨细胞信号通路,包括GEF-H1,NF-κB和AP-1.
在体内研究中使用了正位体小鼠肺癌模型来评估TTFields对瘤负担和TAM表型的影响.

主要成果:

TTFields激活了巨细胞中的GEF-H1,NF-κB和AP-1信号通路.
TTFields通过增加MHC-II和CD80,减少Arg1和提高促炎细胞因子 (CXCL1,IL-6,IL-1β,IL-12p70) 来重新编程M2巨细胞.
在体内,TTFields降低了瘤负担,并在TAM中增加了iNOS表达,表明向炎症状态的转变.

结论:

TTFields直接重编程巨细胞,将它们从免疫抑制M2表型转移到促炎M1表型.
这种TTFields的直接免疫调节作用表明了增强抗瘤免疫力的新机制.
TTFields代表了一种潜在的治疗策略,用于重新教育瘤微环境,以改善癌症治疗结果.

关键词:

在GEF-H1中,GEF-H1是指GEF.我的D8888是什么意思在 NF-κBB 中.治疗瘤的领域 (TTFields)免疫调节免疫调节免疫调节巨细胞的两极分化非小细胞肺癌 (NSCLC) 是一种非小细胞肺癌.

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