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维生素D受体对手MeTC7 抑制PD-L1

Negar Khazan¹, Emily R Quarato², Niloy A Singh¹

¹Wilmot Cancer Institute and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY 14642, USA.

|July 14, 2023

概括

维生素D受体 (VDR) 在血液癌症中调节PD-L1. 一种新的VDR抗剂MeTC7选择性地抑制PD-L1,减少癌症生长并增强抗瘤免疫力.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
在瘤学瘤学.

背景情况:

针对PD-L1/PD-1轴的抗体控制瘤免疫逃避.
小分子抑制剂需要确定可向的PD-L1诱导剂.
维生素D受体 (VDR) 在血液恶性瘤中的PD-L1调节中的作用尚不清楚.

研究的目的:

研究VDR在调节急性髓性白血病 (AML) 和骨髓发育综合征 (MDS) 中PD-L1表达中的作用.
评估MeTC7,一种VDR抗剂,作为PD-L1.1的潜在小分子抑制剂.
在临床前癌症模型中评估MeTC7的疗效和特异性.

主要方法:

染色体免疫沉 (ChIP) 测定和siRNA用于研究VDR-PD-L1调节.
哺乳动物2杂交 (M2H) 试验以确认MeTC7的选择性VDR抑制.
在体外测试细胞活力,克隆性和粘附性.
使用AML异种移植和结直肠癌放射治疗模型的体内研究.

主要成果:

在AML和MDS细胞中,VDR调节PD-L1的表达.
MeTC7选择性地抑制VDR,抑制PD-L1 (但不抑制PD-L2),并降低AML细胞活力,克隆性和异种移植生长.
MeTC7抑制了AML/介酶干细胞的粘附,并增强了癌细胞的细胞增生.
在结直肠癌模型中,MeTC7抑制了PD-L1并增加了内CD8+T细胞.

结论:

MeTC7是一种具有强大的抗癌活性的选择性VDR抑制剂.
MeTC7显示出作为PD-L1.1新型小分子抑制剂的潜力.
MeTC7需要进一步进行癌症治疗的临床研究.

关键词:

在AML,AML就是AML.在M2H测定试验中,M2H测定试验在 MDS MDS 中.在PD-L1中.这是VDR VDR.这种细胞的形成是Efferocytosis.小分子分子小分子维生素D是维生素D的重要组成部分.

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