研究者首先在细胞水平上阐明了ALKBH5调控PD-L1表达的机制:ALKBH5 通过调控PD-L1 mRNA 3‘UTR区m6A 修饰水平,通过YTHDF2调控PD-L1 mRNA 稳定性,从而调控PD-L1表达水平;并进一步通过细胞和动物实验证实了ALKBH5可通过调控ICC细胞PD-L1表达抑制T细胞的杀伤作用。质谱流式分析进一步发现,ICC肿瘤免疫微环境中,ALKBH5过...
抑制ALKBH5是否增强黑色素瘤/结直肠癌的抗PD-1治疗应答,作者运用CRISPR技术敲除了Alkbh5,之后皮下接种,在B16模型中在第1天和第四天注射GVAX(26)(诱导T细胞抗肿瘤效应),在第6、9、12天用抗PD-L1治疗小鼠;在CT26模型中,在第11、14...
PD-L1胃癌目的:胃癌(gastric cancer,GC)的程序性死亡配体1(Programmed death-ligand1,PD-L1)免疫检查点阻断治疗疗效欠佳,N6-甲基腺苷(N6-methyladenosine,m6A)修饰可调节PD-L1表达,m6A去甲基化酶ALKB同源蛋白5(a-ketoglutarate-dependent dioxygenase homolog5,ALKBH5)是该修饰调节过程中的重要靶点.通过检测ALKBH5,PD...
H Pearson correlation coefficient analysis of ALKBH5 and PD-L1 expression in 40 cases of NSCLC. *P < 0.05; **P < 0.01; ***P < 0.001; NS, not significant Full size image Kaplan–Meier analysis showed that increased ALKBH5 expression was associated with shorter overall survival ...
Through the ALKBH5-PD-L1 axis, it maintains the expression of PD-L1 in tumor cells, suppressing T-cell proliferation and cytotoxicity, and regulating the occurrence of ICC [68]. Liver cancer stem cells (LCSCs) are closely associated with the treatment and recurrence of LC. ALKBH5 regulates ...
癌中FGL1表达水平对免疫微环境和免疫治疗疗效的影响本部分研究目的:1.利用公共数据库,分析接受PD-1/PD-L1抑制剂治疗的膀胱癌患者,应答组与无应答组中多个免疫检查点相对表达水平,明确FGL1在应答组与无应答组中差异表达,研究膀胱癌中FGL1对PD-1/PD-L1抑制剂治疗疗效和预后的影响;2.检测PD-1/PD-L1抑制剂治疗...
These data suggest that the combination of anti-PD-1 therapy and ALKBH5 inhibition may be a promising treatment strategy in glioma. 展开 关键词: RNA METHYLATION EXPRESSION NIVOLUMAB PD-L1 CMTM6 DOI: 10.1038/s41420-022-01286-w 收藏 引用 批量引用 报错 分享 ...
中国医学科学院团队2022年在《细胞研究》发表的工作揭示,ALKBH5与免疫检查点PD-L1存在直接互作,可能影响肿瘤免疫逃逸机制。 当前研究存在三个争议焦点:第一,检测手段的局限性导致难以精确定量细胞内ALKBH5活性,现有抗体普遍存在交叉反应问题;第二,动物模型无法完全模拟人类疾病中RNA修饰的动态变化,基因敲除可能引发代偿...
33 Tang W., et al. ALKBH5 promotes PD-L1-mediated immune escape through m6A modification of ZDHHC3 in glioma Cell death discovery, 8 (2022), p. 497 View in ScopusGoogle Scholar Cited by (0)# These authors have contributed equally to this work. ...
PD-L1 Programmed cell death ligand 1 Introduction Colorectal cancer is one of the most common cancers worldwide, ranking third for incidence and fifth for mortality rates [1]. Due to the insidious onset of CRC, approximately 25% of patients are already at an advanced stage when initially diagn...