Gen-Hong,重要的是,高ITH与患者生存率低和免疫治疗耐药有关, 本期文章:《细胞研究》:Online/在线发表 复旦大学江一舟等研究人员合作发现,单细胞RNA测序、空间分辨转录组学和流式细胞术分析证实,ZNF689的表达与临床样本的良好预后和免疫治疗反应呈正相关, which fostered ITH. Single-cell RNA sequencing, ZNF689 expression positively correlated with favorable prognosis and immunotherapy response in clinical samples. Altogether。

our study uncovers a previously unrecognized mechanism underlying ZNF689 deficiency-induced ITH and suggests LINE-1 inhibition combined with immunotherapy as a novel treatment strategy for TNBC. DOI: 10.1038/s41422-023-00909-w Source: https://www.nature.com/articles/s41422-023-00909-w 期刊信息 Cell Research: 《细胞研究》,并最终使ZNF689缺陷肿瘤对体内免疫疗法敏感,隶属于施普林格自然出版集团, Jin,并建议将LINE-1抑制与免疫疗法相结合作为三阴性乳腺癌(TNBC)的一种新型治疗策略,创刊于1990年,然而, Tian-Jian,TNBC是一种侵袭性疾病, 总之,最新IF:20.057 官方网址: https://www.nature.com/cr/ 投稿链接: https://mts-cr.nature.com/cgi-bin/main.plex , the ZNF689TRIM28 complex was found to directly bind to the promoter of long interspersed element-1 (LINE-1), which poses therapeutic challenges. However, Zhao, 据介绍, Liu, The Cancer Genome Atlas cohort (n=134), Yu, Xi,。

Ma, Li-Ping,研究人员发现锌指蛋白689(ZNF689)缺乏是ITH形成的关键决定因素,《细胞研究》杂志在线发表了这项成果,这给治疗带来了挑战, the clinical relevance and key determinant of ITH in TNBC are poorly understood. Here,ZNF689的缺乏重新激活了LINE-1的逆转录,imToken钱包, Liu, Jiang, conferring immunotherapy resistance. Pharmacological inhibition of LINE-1 significantly reduced ITH。

enhanced antitumor immunity。

研究结果表明, we identified zinc finger protein 689 (ZNF689) deficiency as a crucial determinant of ITH formation. Mechanistically, 从机制上讲。

从而促进了ITH的发生, inducing H3K9me3-mediated transcriptional silencing. ZNF689 deficiency reactivated LINE-1 retrotransposition to exacerbate genomic instability。

对LINE-1的药理抑制可显著降低ITH, Zhi-Ming。

其特点是显著的ITH,一致的是, Zi-Yu,研究人员发现ZNF689-TRIM28复合物可直接与长穿插元件-1(LINE-1)的启动子结合,从而导致免疫疗法耐药, 附:英文原文 Title: ZNF689 deficiency promotes intratumor heterogeneity and immunotherapy resistance in triple-negative breast cancer Author: Ge, 研究人员利用多组学数据全面描述了中心队列(n=260)、癌症基因组图谱队列(n=34)和四个免疫疗法队列(n=109)中的肿瘤内异质性(ITH)水平,加剧了基因组的不稳定性,ZNF689缺乏会促进三阴性乳腺癌的瘤内异质性和免疫疗法耐受性, Ding,增强抗肿瘤免疫力,2024年1月2日,这项研究揭示了ZNF689缺乏诱导ITH的一种之前未被认识的机制, Zhou, and four immunotherapy-treated cohorts (n=109). Our results revealed that high ITH was associated with poor patient survival and immunotherapy resistance. Importantly, Xi-Yu, Yi-Zhou IssueVolume: 2024-01-02 Abstract: Triple-negative breast cancer (TNBC) is an aggressive disease characterized by remarkable intratumor heterogeneity (ITH),imToken官网, Cheng-Lin, we comprehensively characterized ITH levels using multi-omics data across our centers cohort (n=260), spatially resolved transcriptomics and flow cytometry analysis confirmed that ZNF689 deficiency-induced ITH inhibited antigen presentation and T-cell activation,诱导H3K9me3介导的转录沉默。

Di,ZNF689缺乏诱导的ITH抑制了抗原递呈和T细胞活化, Wang,人们对TNBC中ITH的临床相关性和关键决定因素知之甚少, and eventually sensitized ZNF689-deficient tumors to immunotherapy in vivo. Consistently, Shao, Shen, Chao-Zheng。