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正确刺激CD28H臂NK细胞对瘤细胞的正确刺激

Raphaëlle Leau¹, Pierre Duplouye¹, Virginie Huchet¹

¹Center for Research in Transplantation and Translational Immunology, Nantes Université, CHU Nantes, INSERM, UMR 1064, Nantes, France.

European journal of immunology

|August 5, 2024

概括

瘤逃避涉及HHLA2,一种蛋白质在PDL-1阴性瘤中过度表达. 用特定抗体向CD28H激活NK细胞,增强其抗癌能力并绕过瘤防御.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞生物学细胞生物学

背景情况:

瘤逃避是一个复杂的过程,通常涉及免疫检查点蛋白质.
HERV-H LTR-关联2 (HHLA2) 是一种新的B7家族成员,涉及瘤免疫逃避,特别是在PD-L1阴性瘤中.
HHLA2与CD28H进行共刺激或KIR3DL3进行抑制,从而影响T细胞和NK细胞的反应.

研究的目的:

调查针对CD28H的潜力,作为增强自然杀手 (NK) 细胞介导的抗瘤免疫力的策略.
为了比较两个不同的单克隆抗体 (mAbs) 针对NK细胞上的CD28H受体的疗效.

主要方法:

流细胞计和流量测试以测量NK细胞激活.
细胞毒性测定对造血细胞系进行检测.
单细胞RNA测序 (scRNA-seq) 用于分析清细胞脏癌 (ccRCC) 中的瘤微环境组成.

主要成果:

将CD28H定位在特定的表位上诱导了强大的流和NK细胞激活.
激活的NK细胞表现出对癌细胞的增强细胞毒性活性.
CD28H激活的NK细胞表现出克服HHLA2和HLA-E介导的抑制信号的能力.
scRNA-seq揭示了CD28H+ NK细胞在HHLA2+ ccRCC瘤中的透,这表明一个可向的群体.

结论:

特定的抗CD28H单克隆抗体可以有效地激活NK细胞并增强其抗瘤功能.
这种方法提供了一种有希望的策略,以克服某些癌症中HHLA2-介导的免疫逃避.
向CD28H代表了HHLA2表达瘤的潜在治疗途径,包括清细胞细胞癌.

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