Wang Guanwu, Liu Dong, Al-Masri Tarick M, Otto Carlos C, Siveke Jens, Lang Sven A, Ulmer Tom F, Olde Damink Steven Wm, Luedde Tom, Dahl Edgar, Neumann Ulf P, Heij Lara R, Bednarsch Jan
Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
University of Applied Science Aachen, Aachen, Germany.
J Clin Exp Hepatol. 2025 Mar-Apr;15(2):102460. doi: 10.1016/j.jceh.2024.102460. Epub 2024 Nov 26.
Due to malnutrition and tumor cachexia, body composition (BC) is frequently altered and known to adversely affect short- and long-term results in patients with cholangiocarcinoma (CCA). Here, we explored immune cell populations in the tumor and liver of CCA patients with respect to BC.
A cohort of 96 patients who underwent surgery for CCA was investigated by multiplexed immunofluorescence (MIF) techniques with computer-based analysis on whole-tissue slide scans to quantify and characterize immune cells in normal liver and tumor regions. BC was characterized by obesity, sarcopenia, myosteatosis, visceral obesity and sarcopenic obesity. Associations between BC and immune cell populations were determined by univariate and multivariable binary logistic regressions.
BC was frequently altered in intrahepatic CCA (iCCA, n = 48), with 47.9% of the patients showing obesity, 70.8% sarcopenia, 18.8% sarcopenic obesity, 58.3% myosteatosis and 54.2% visceral obesity as well as in perihilar CCA (pCCA, n = 48) with 45.8% of the patients showing obesity, 54.0 sarcopenia, 14.6% sarcopenic obesity, 47.9% myosteatosis and 56.3% visceral obesity. From an immune cell perspective, independent associations within the tumor compartment were observed for iCCA (myosteatosis: TIM-3+CD8+cells; obesity: PD-1+TIM-3+CD4+cells) and for pCCA (myosteatosis: PD-L2+CD68-cells and CD4+cells). Further, independent associations were observed within the normal liver parenchyma for iCCA (visceral obesity: PD-1+PD-L1+PD-L2+CD68+cells) and for pCCA (sarcopenia: CD68+cells and TIM-3+CD8+cells; visceral obesity: ICOS+-TIGIT+CD8+cells and sarcopenic obesity: PD-1+PD-L1+PD-L2+CD8+cells).
This is the first systematic analysis of the association of BC and immune cells in cholangiocarcinoma showing a strong association between BC and distinct immune cell populations within the tumor itself as well as within the normal parenchyma.
由于营养不良和肿瘤恶病质，胆管癌（CCA）患者的身体组成（BC）经常发生改变，且已知会对患者的短期和长期预后产生不利影响。在此，我们探讨了CCA患者肿瘤和肝脏中的免疫细胞群体与身体组成的关系。
采用多重免疫荧光（MIF）技术，对96例行CCA手术的患者进行研究，并通过基于计算机的全组织切片扫描分析，以量化和表征正常肝脏和肿瘤区域的免疫细胞。身体组成通过肥胖、肌肉减少症、肌少脂性肥胖、内脏肥胖和肌少性肥胖来表征。身体组成与免疫细胞群体之间的关联通过单变量和多变量二元逻辑回归确定。
肝内CCA（iCCA，n = 48）患者的身体组成经常发生改变，47.9%的患者表现为肥胖，70.8%为肌肉减少症，18.8%为肌少性肥胖，58.3%为肌少脂性肥胖，54.2%为内脏肥胖；肝门周围CCA（pCCA，n = 48）患者中，45.8%的患者表现为肥胖，54.0%为肌肉减少症，14.6%为肌少性肥胖，47.9%为肌少脂性肥胖，56.3%为内脏肥胖。从免疫细胞角度来看，在肿瘤区域内，iCCA（肌少脂性肥胖：TIM-3+CD8+细胞；肥胖：PD-1+TIM-3+CD4+细胞）和pCCA（肌少脂性肥胖：PD-L2+CD68-细胞和CD4+细胞）存在独立关联。此外，在正常肝实质内，iCCA（内脏肥胖：PD-1+PD-L1+PD-L2+CD68+细胞）和pCCA（肌肉减少症：CD68+细胞和TIM-3+CD8+细胞；内脏肥胖：ICOS+-TIGIT+CD8+细胞；肌少性肥胖：PD-1+PD-L1+PD-L2+CD8+细胞）也存在独立关联。
这是首次对胆管癌中身体组成与免疫细胞的关联进行系统分析，结果显示身体组成与肿瘤本身以及正常实质内不同的免疫细胞群体之间存在密切关联。
