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巨细胞转录基因变化是由基于阿尔法病毒的癌症免疫疗法载体驱动的

Ksenija Korotkaja¹, Darija Lapina¹, Zhanna Rudevica¹

¹Cancer Gene Therapy Group, Latvian Biomedical Research and Study Centre, Ratsupites Str. 1 k. 1, Riga LV-1067, Latvia.

Journal of immunology research

|June 23, 2025

概括

病毒免疫疗法载体可以将与瘤相关的巨细胞 (TAMs) 重编为抗癌M1表型. 塞姆利基森林病毒 (SFV) 载体改变癌细胞,影响巨细胞重编程,并可能增强癌症治疗.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
癌症生物学癌症生物学

背景情况:

与瘤相关的巨细胞 (TAMs) 经常采用一种亲瘤的M2表型,阻碍癌症治疗.
将TAM重新编程为使用病毒免疫疗法载体的抗瘤M1表型是一种有希望的策略.
了解病毒载体对巨细胞重编程的机制对于有效的癌症治疗至关重要.

研究的目的:

为了研究由塞姆利基森林病毒 (SFV) 载体诱导的巨细胞中的转录基因变化.
确定SFV介导的基因传递到癌细胞是如何影响巨细胞的两极分化.
探索阿尔法病毒载体对重编程巨细胞向抗癌表型的潜力.

主要方法:

鼠乳腺癌细胞被携带TNFα或IFNγ基因的SFV载体感染.
来自受感染癌细胞的条件介质被用于治疗骨髓衍生巨细胞 (BMDMs).
对接受治疗的BMDM进行了转录组分析 (RNA测序),以评估基因表达变化.

主要成果:

被SFV感染的癌细胞调节了细胞因子配置,减少了免疫抑制和增加了炎症.
用SFV受条件介质对巨细胞进行治疗,可提高与抗原呈现,干扰素反应和M1极化相关的基因的调节.
SFV/IFNγ 抑制了前瘤源途径 (血管生成,糖解,ECM重塑) 和增加了细胞毒性T淋巴细胞吸引剂.
SFV载体对巨细胞的PD-L1 (Cd274) 表达进行了上调.

结论:

阿尔法病毒介导的基因传递到癌细胞可以诱导巨细胞的炎症反应,将它们重新编程为抗癌M1表型.
SFV载体显示出调节瘤微环境和增强抗瘤免疫力的潜力.
将SFV/IFNγ与免疫检查点抑制剂相结合,可以通过抵消病毒诱导的抑制信号来改善治疗结果.

关键词:

塞米利基森林病毒艾尔法病毒 (alphavirus) 是一种来自骨髓的巨细胞.细胞因子基因传递瘤微环境是一个微环境.

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