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

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

doi:10.1016/j.jceh.2024.102460

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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+PDL2+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 fi rst 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.

Original language	English
Article number	102460
Number of pages	21
Journal	Journal of Clinical and Experimental Hepatology
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.jceh.2024.102460
Publication status	Published - 1 Mar 2025

Keywords

cholangiocellular carcinoma
immune cells
body composition
oncological outcome
SARCOPENIC OBESITY
CANCER
TIM-3
PREVALENCE
RESISTANCE
TARGET
PHASE

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Wang, G., Liu, D., Al-Masri, T. M., Otto, C. C., Siveke, J., Lang, S. A., Ulmer, T. F., Damink, S. W. M. O., Luedde, T., Dahl, E., Neumann, U. P., Heij, L. R., & Bednarsch, J. (2025). Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma. Journal of Clinical and Experimental Hepatology, 15(2), Article 102460. https://doi.org/10.1016/j.jceh.2024.102460

@article{09eb89f7175b4c25a5f21c6187c01d32,

title = "Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma",

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+PDL2+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 fi rst 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.",

keywords = "cholangiocellular carcinoma, immune cells, body composition, oncological outcome, SARCOPENIC OBESITY, CANCER, TIM-3, PREVALENCE, RESISTANCE, TARGET, PHASE",

author = "Guanwu Wang and Dong Liu and Al-Masri, {Tarick M.} and Otto, {Carlos C.} and Jens Siveke and Lang, {Sven A.} and Ulmer, {Tom F.} and Damink, {Steven W. M. Olde} and Tom Luedde and Edgar Dahl and Neumann, {Ulf P.} and Heij, {Lara R.} and Jan Bednarsch",

year = "2025",

month = mar,

day = "1",

doi = "10.1016/j.jceh.2024.102460",

language = "English",

volume = "15",

journal = "Journal of Clinical and Experimental Hepatology",

issn = "0973-6883",

publisher = "Elsevier B.V.",

number = "2",

}

Wang, G, Liu, D, Al-Masri, TM, Otto, CC, Siveke, J, Lang, SA, Ulmer, TF, Damink, SWMO, Luedde, T, Dahl, E, Neumann, UP, Heij, LR & Bednarsch, J 2025, 'Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma', Journal of Clinical and Experimental Hepatology, vol. 15, no. 2, 102460. https://doi.org/10.1016/j.jceh.2024.102460

TY - JOUR

T1 - Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma

AU - Wang, Guanwu

AU - Liu, Dong

AU - Al-Masri, Tarick M.

AU - Otto, Carlos C.

AU - Siveke, Jens

AU - Lang, Sven A.

AU - Ulmer, Tom F.

AU - Damink, Steven W. M. Olde

AU - Luedde, Tom

AU - Dahl, Edgar

AU - Neumann, Ulf P.

AU - Heij, Lara R.

AU - Bednarsch, Jan

PY - 2025/3/1

Y1 - 2025/3/1

N2 - 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+PDL2+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 fi rst 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.

AB - 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+PDL2+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 fi rst 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.

KW - cholangiocellular carcinoma

KW - immune cells

KW - body composition

KW - oncological outcome

KW - SARCOPENIC OBESITY

KW - CANCER

KW - TIM-3

KW - PREVALENCE

KW - RESISTANCE

KW - TARGET

KW - PHASE

U2 - 10.1016/j.jceh.2024.102460

DO - 10.1016/j.jceh.2024.102460

M3 - Article

SN - 0973-6883

VL - 15

JO - Journal of Clinical and Experimental Hepatology

JF - Journal of Clinical and Experimental Hepatology

IS - 2

M1 - 102460

ER -

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

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Keywords

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