胆管癌机体组成对肿瘤和正常肝实质免疫细胞群的影响

IF 3.3 Q2 GASTROENTEROLOGY & HEPATOLOGY Journal of Clinical and Experimental Hepatology Pub Date : 2025-03-01 Epub Date: 2024-11-26 DOI:10.1016/j.jceh.2024.102460

Guanwu Wang, Dong Liu, Tarick M Al-Masri, Carlos C Otto, Jens Siveke, Sven A Lang, Tom F Ulmer, Steven Wm Olde Damink, Tom Luedde, Edgar Dahl, Ulf P Neumann, Lara R Heij, Jan Bednarsch

{"title":"胆管癌机体组成对肿瘤和正常肝实质免疫细胞群的影响","authors":"Guanwu Wang, Dong Liu, Tarick M Al-Masri, Carlos C Otto, Jens Siveke, Sven A Lang, Tom F Ulmer, Steven Wm Olde Damink, Tom Luedde, Edgar Dahl, Ulf P Neumann, Lara R Heij, Jan Bednarsch","doi":"10.1016/j.jceh.2024.102460","DOIUrl":null,"url":null,"abstract":"Background: 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.Methods: 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.Results: 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).Conclusion: 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.","PeriodicalId":15479,"journal":{"name":"Journal of Clinical and Experimental Hepatology","volume":"15 2","pages":"102460"},"PeriodicalIF":3.3000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697564/pdf/","citationCount":"0","resultStr":"{\"title\":\"Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma.\",\"authors\":\"Guanwu Wang, Dong Liu, Tarick M Al-Masri, Carlos C Otto, Jens Siveke, Sven A Lang, Tom F Ulmer, Steven Wm Olde Damink, Tom Luedde, Edgar Dahl, Ulf P Neumann, Lara R Heij, Jan Bednarsch\",\"doi\":\"10.1016/j.jceh.2024.102460\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: 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.Methods: 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.Results: 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).Conclusion: 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.\",\"PeriodicalId\":15479,\"journal\":{\"name\":\"Journal of Clinical and Experimental Hepatology\",\"volume\":\"15 2\",\"pages\":\"102460\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697564/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical and Experimental Hepatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jceh.2024.102460\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical and Experimental Hepatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.jceh.2024.102460","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：由于营养不良和肿瘤恶病质，体成分（BC）经常发生改变，并且已知对胆管癌（CCA）患者的短期和长期结果产生不利影响。在这里，我们探讨了CCA患者肿瘤和肝脏中与BC相关的免疫细胞群。方法：采用多路免疫荧光（MIF）技术对96例接受CCA手术的患者进行队列研究，并对全组织切片扫描进行计算机分析，以量化和表征正常肝脏和肿瘤区域的免疫细胞。BC以肥胖、肌肉减少症、肌骨化症、内脏肥胖和肌肉减少性肥胖为特征。通过单变量和多变量二元logistic回归确定BC和免疫细胞群之间的关联。结果：BC在肝内CCA （iCCA, n = 48）中经常改变，其中47.9%的患者表现为肥胖，70.8%的患者表现为肌肉减少症，18.8%的患者表现为肌肉减少症，58.3%的患者表现为肌骨化症，54.2%的患者表现为内脏型肥胖；在肝门周围CCA （pCCA, n = 48）中，45.8%的患者表现为肥胖，54.0%的患者表现为肌肉减少症，14.6%的患者表现为肌肉减少症，47.9%的患者表现为肌骨化症，56.3%的患者表现为内脏型肥胖。从免疫细胞的角度来看，在iCCA(肌骨化病：TIM-3+CD8+细胞；肥胖：PD-1+TIM-3+CD4+细胞)和pCCA（肌骨化症：PD-L2+ cd68细胞和CD4+细胞）。此外，在正常肝实质中观察到iCCA（内脏肥胖：PD-1+PD-L1+PD-L2+CD68+细胞）和pCCA(肌肉减少：CD68+细胞和TIM-3+CD8+细胞；内脏型肥胖：ICOS+-TIGIT+CD8+细胞；肌少型肥胖：PD-1+PD-L1+PD-L2+CD8+细胞)。结论：这是对胆管癌中BC和免疫细胞相关性的首次系统分析，显示了BC和肿瘤本身以及正常实质内不同的免疫细胞群之间的强相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊