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针对肝细胞癌的向性免疫细胞治疗,使用扩大肝单核细胞衍生的自然杀手细胞

Xin Hu¹, Yifang Shui², Seiichi Shimizu³

¹Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

Neoplasia (New York, N.Y.)

|October 2, 2024

概括

来自肝移植的自然杀手 (NK) 细胞为肝细胞癌 (HCC) 提供了一种新的治疗方法. 这些扩展的肝脏衍生的NK细胞 (LMNC-NK) 与外周血液NK细胞相比,显示出增强的抗瘤活性.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞疗法细胞疗法

背景情况:

自然杀手 (NK) 细胞对于抗癌免疫是至关重要的,但在肝细胞癌 (HCC) 患者中经常受到损害.
肝细胞癌 (HCC) 仍然是一个重大的健康挑战,需要新的治疗策略.
使用NK细胞的现有细胞疗法由于细胞的可用性和功能而面临限制.

研究的目的:

为了研究 NK 细胞的治疗潜力,来源于供体肝移植 perfusate 来进行 HCC 治疗.
描述和比较来自肝脏的NK细胞 (LMNC-NK) 与周围血液NK细胞 (PBMC-NK) 的功能性质.
在临床前HCC模型中评估LMNC-NK细胞采用转移的疗效.

主要方法:

从供体肝移植透物 (LMNC-NK细胞) 中分离和扩张NK细胞.
对LMNC-NK和PBMC-NK细胞进行比较分析,包括细胞毒性测定,细胞因子概况 (granzyme B,CD107a,TNF-α,IFN-γ) 和受体表达.
RNA测序 (RNA-seq) 和定量逆转录聚合酶连锁反应 (qRT-PCR) 用于识别差异性基因表达.
在实验室对HepG-2-Luc HCC细胞的疗效测试和在体内评估,使用一种正位素的小鼠HCC模型.

主要成果:

与PBMC-NK细胞相比,LMNC-NK细胞更丰富,可以显著扩展 (33.8±54.4倍).
扩展的LMNC-NK细胞表现出增强的细胞毒性,细胞因子的产生和细胞毒性受体的表达.
RNA-seq揭示了显著的基因表达差异,LMNC-NK细胞中的上调基因参与MAPK信号传递和细胞分化.
与PBMC-NK细胞相比,LMNC-NK细胞在体外和体内表现出较高的抗瘤疗效,在瘤透淋巴细胞中表达的CD69更高.

结论:

来自肝移植的NK细胞是HCC细胞治疗的有希望和有效来源.
LMNC-NK细胞具有卓越的细胞毒性功能和抗瘤活性,使其成为一个有价值的治疗候选者.
扩大的LMNC-NK细胞的采用转移为T细胞耐火性HCC提供了一种新且有效的治疗策略.

关键词:

收养免疫疗法是一种免疫疗法.肝细胞癌是肝细胞癌.肝脏单核细胞是一种肝脏单核细胞.在 NK 细胞中,NK 细胞是 NK 细胞.周围血液中的单核细胞.

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