该研究表明， 活化的 ATF6α 是一种肝肿瘤驱动因子，可限制免疫监视，其可作为免疫检查点阻断 （ICB） 疗法响应的潜在分层标志物，也是肝细胞癌的治疗新 靶点。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 肝细胞癌 （HCC）， 主要源自慢性肝炎中恶性转化的肝细胞，其 占原发性肝癌的 80% - 85%。尽管免疫疗法的进步提高了肝细胞癌患者的生存率，但复杂的 遗传、代谢和炎症相互作用仍是有效治疗的障碍。 肝细胞癌浸润淋巴细胞表达耗竭标志物 （例如 PD-1、CTLA-4） ，导致预后不良。免疫检查点阻断 （阿特珠单抗） 和血管内皮生长因子 （VEGF） 阻断 （贝 伐珠单抗） 以改善 T 细胞介导的肿瘤监视是不可切除肝细胞癌的标准治疗方法。然而，肝细胞癌中的代谢重编程 （包括葡萄糖剥夺和肿瘤内缺氧环境） ，会降 低抗肿瘤治疗效果并增强恶性程度。因此，需要新的策略来克服与代谢相关的肿瘤逃逸和免疫抑制。 2026 年 2 月 4 日， 德国癌症研究中心 Li Xin 作为第一作者，在国际顶尖学术期刊 Nature 上发表了题为： Activated ATF6α is a hepatic tumour driver ...

Core Viewpoint - The article discusses the role of the gut microbiome, specifically the bacterium Catenibacterium mitsuokai, in promoting hepatocellular carcinoma (HCC) through mechanisms involving gut barrier disruption and metabolic product secretion [2][3][5]. Group 1: Research Findings - A new carcinogenic gut bacterium, Catenibacterium mitsuokai, has been identified, which promotes the development of HCC by binding to hepatocytes and generating quinolinic acid [3][6]. - Catenibacterium mitsuokai is enriched in the feces and tumors of HCC patients, and it accelerates the carcinogenesis process in both conventional and germ-free mice [5][10]. - The bacterium disrupts the gut barrier and transfers to the liver, where it adheres to HCC cells via the interaction of its surface protein Gtr1/RagA with the γ-catenin receptor on cancer cells [6][10]. Group 2: Mechanistic Insights - The tumor-promoting effect of Catenibacterium mitsuokai is dependent on its secretion of the metabolite quinolinic acid [6][9]. - Quinolinic acid binds to the TIE2 receptor on HCC cells, activating the downstream oncogenic PI3K/AKT pathway, thereby facilitating the progression of liver cancer [6][9].

Core Viewpoint - The research identifies a class of micropeptides related to hepatocellular carcinoma (HCC) and reveals their regulatory mechanisms on mitochondrial RNA processing, providing new insights for cancer diagnosis and treatment [3][8]. Group 1: Research Findings - A new study published in Molecular Cell describes micropeptides associated with HCC and their role in modulating mitochondrial RNA processing machinery [3]. - The research team utilized a novel ultrafiltration tandem mass spectrometry method to identify a significant number of micropeptides in clinical HCC samples [4]. - One specific micropeptide, mitochondrial RNase P inhibitory peptide (MRPIP), derived from long non-coding RNA (lncRNA), inhibits the progression of HCC by regulating mitochondrial RNA processing [4][5]. Group 2: Mechanism of Action - MRPIP interacts with the R25 residue of HSD17B10, preventing the assembly of the mitochondrial RNase P (mtRNase P) complex, which disrupts HSD17B10 oligomerization and subsequent formation of the HSD17B10-TRMT10C subcomplex [5]. - This disruption leads to disturbances in post-transcriptional RNA processing, translation, and energy generation in mitochondria, thereby inhibiting cancer progression [5]. Group 3: Implications for Treatment - The research generated a functional peptide of 20 amino acids from the MRPIP sequence, which significantly inhibits the progression of HCC both in vitro and in vivo [6].