Chen Zhixuan, Song Honghu, Tang Junrui, Liu Jiao, Xia Lina
School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
Discov Oncol. 2024 Nov 29;15(1):726. doi: 10.1007/s12672-024-01628-3.
Cholangiocarcinoma (CHOL) is a rare cancer with low survival rates. Despite advances in precision medicine targeting molecular subtypes, the immune subtypes of CHOL remain poorly understood. This study aimed to identify immune subtypes of CHOL and investigate their implications in the metabolic regulation of macrophage functions in inflammation.
We conducted a comprehensive analysis of transcriptome and single-cell sequencing data from multiple databases to classify the immune subtypes of CHOL. Immune cell infiltration within the tumor microenvironment (TME) and the metabolic pathways involved in macrophage activation and polarization were also analyzed.
Two distinct immune subtypes, immune-infiltrated CS1 and immune-depleted CS2, were identified in CHOL. CS1 exhibited a highly active TME with substantial immune cell infiltration, including macrophages, and activation of immune-related signaling pathways, such as inflammatory and interferon pathways. In contrast, CS2 was characterized by a deficiency in immune components and poorer prognosis. Metabolic regulation of macrophages, particularly the downregulation of oxidative phosphorylation in CS1, suggested a shift towards glycolysis as an energy source for activated macrophages, contributing to the immune-responsive phenotype observed in CS1. Additionally, the oncogenic role of DLX5 in CHOL was revealed, with potential impacts on macrophage functions in inflammation.
This study provides insights into immune subtype classification, novel biomarker identification, and the metabolic regulation of macrophage functions in CHOL. Understanding macrophage metabolic reprogramming within immune subtypes may contribute to the development of targeted immunotherapies for CHOL.
胆管癌（CHOL）是一种生存率较低的罕见癌症。尽管针对分子亚型的精准医学取得了进展，但胆管癌的免疫亚型仍知之甚少。本研究旨在识别胆管癌的免疫亚型，并研究它们在炎症中巨噬细胞功能代谢调节中的意义。
我们对来自多个数据库的转录组和单细胞测序数据进行了全面分析，以对胆管癌的免疫亚型进行分类。还分析了肿瘤微环境（TME）内的免疫细胞浸润以及参与巨噬细胞活化和极化的代谢途径。
在胆管癌中鉴定出两种不同的免疫亚型，免疫浸润型CS1和免疫耗竭型CS2。CS1表现出高度活跃的TME，有大量免疫细胞浸润，包括巨噬细胞，并激活了免疫相关信号通路，如炎症和干扰素通路。相比之下，CS2的特征是免疫成分缺乏且预后较差。巨噬细胞的代谢调节，特别是CS1中氧化磷酸化的下调，表明向糖酵解转变作为活化巨噬细胞的能量来源，有助于在CS1中观察到的免疫反应表型。此外，还揭示了DLX5在胆管癌中的致癌作用，对炎症中巨噬细胞功能有潜在影响。
本研究为胆管癌的免疫亚型分类、新型生物标志物鉴定以及巨噬细胞功能的代谢调节提供了见解。了解免疫亚型内巨噬细胞的代谢重编程可能有助于开发针对胆管癌的靶向免疫疗法。
