Dynamic contrast-enhanced MRI and tumor microenvironment in hepatocellular carcinoma: exploratory analysis of CD3 + TILs, PD-L1, and glypican-3
5 affiliations
- 1Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
- 2Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo, Italy
- 3Department of Pathology, University of Leipzig, Leipzig, Germany
- 4Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig, Leipzig, Germany
- 5Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
Abstract
Objectives: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is the clinical diagnostic standard in hepatocellular carcinoma (HCC), but its association with the tumor microenvironment is not fully characterized. In this study, we investigated correlations between DCE-MRI parameters and immunohistochemistry features of HCC.
Materials and methods: Forty patients, six women and 34 men aged 61.5 ± 10.1 years (mean ± standard deviation) with histologically confirmed HCC were included. DCE-MRI with Gd-EOB-DTPA was performed before surgery, and quantitative parameters were calculated to reflect arterial wash-in, portal venous wash-out and hepatobiliary uptake. Pathological specimens were analyzed for programmed death ligand 1 (PD-L1), glypican-3, CD3+ tumor- and stromal-infiltrating lymphocytes, CD68 and CD34.
Results: CD3+ stromal lymphocytes infiltration was inversely correlated with the arterial wash-in (r = -0.47; adjusted p-value = 0.025) and several post-arterial parameters. For the other TME components, only exploratory correlations were identified, none of which were statistically significant after adjustment for multiple testing. CD3+ tumoral infiltration lymphocytes with arterial wash-in (r = -0.35) and transitional phase relative signal intensity (SI) (r = 0.35). Native SI was inversely correlated with PD-L1 (r = -0.32). Difference in SI between the transitional and portal phase correlated with glypican-3 expression (r = 0.32).
Conclusion: DCE-MRI shows a moderate association with stromal infiltrating lymphocytes (CD3⁺ SIL) in HCC. Associations with other components of the TME, including tumor-infiltrating lymphocytes (CD3⁺ TIL), PD-L1 and Glypican-3 expression, were observed at uncorrected thresholds, but did not remain statistically significant after correction for multiple testing.
Key Points: Question DCE-MRI constitutes the cornerstone of HCC diagnosis. Is quantitative assessment of wash-in, wash-out and hepatobiliary uptake associated with non-invasive characterization of the TME?
Findings CD3⁺ SIL were associated with tumor wash-in and wash-out parameters. Exploratory associations involving CD3⁺ TIL, PD-L1, and glypican-3 lost significance after multiple-testing adjustment.
Relevance statement Quantitative DCE-MRI parameters may provide additional non-invasive information regarding tumor tissue characteristics and the tumor microenvironment of HCC.
Graphical Abstract:
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BibTeX
@article{romeo2026dynamic,
title = {{Dynamic contrast-enhanced MRI and tumor microenvironment in hepatocellular carcinoma: exploratory analysis of CD3 + TILs, PD-L1, and glypican-3}},
author = {Daniele Romeo and Jacob Jalil Hassan and Felix Pfister and Anne-Kathrin Höhn and Hans-Michael Tautenhahn and Daniel Seehofer and Uwe Scheuermann and Florian van Bömmel and Timm Denecke and Hans-Jonas Meyer},
journal = {European Radiology Experimental},
year = {2026},
month = nov,
doi = {10.1186/s41747-026-00834-8},
url = {https://doi.org/10.1186/s41747-026-00834-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dynamic contrast-enhanced MRI and tumor microenvironment in hepatocellular carcinoma: exploratory analysis of CD3 + TILs, PD-L1, and glypican-3
AU - Daniele Romeo
AU - Jacob Jalil Hassan
AU - Felix Pfister
AU - Anne-Kathrin Höhn
AU - Hans-Michael Tautenhahn
AU - Daniel Seehofer
AU - Uwe Scheuermann
AU - Florian van Bömmel
AU - Timm Denecke
AU - Hans-Jonas Meyer
PY - 2026
DA - 2026/11/03
JO - European Radiology Experimental
DO - 10.1186/s41747-026-00834-8
UR - https://doi.org/10.1186/s41747-026-00834-8
AB - Objectives: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is the clinical diagnostic standard in hepatocellular carcinoma (HCC), but its association with the tumor microenvironment is not fully characterized. In this study, we investigated correlations between DCE-MRI parameters and immunohistochemistry features of HCC. Materials and methods: Forty patients, six women and 34 men aged 61.5 ± 10.1 years (mean ± standard deviation) with histologically confirmed HCC were included. DCE-MRI with Gd-EOB-DTPA was performed before surgery, and quantitative parameters were calculated to reflect arterial wash-in, portal venous wash-out and hepatobiliary uptake. Pathological specimens were analyzed for programmed death ligand 1 (PD-L1), glypican-3, CD3+ tumor- and stromal-infiltrating lymphocytes, CD68 and CD34. Results: CD3+ stromal lymphocytes infiltration was inversely correlated with the arterial wash-in (r = -0.47; adjusted p-value = 0.025) and several post-arterial parameters. For the other TME components, only exploratory correlations were identified, none of which were statistically significant after adjustment for multiple testing. CD3+ tumoral infiltration lymphocytes with arterial wash-in (r = -0.35) and transitional phase relative signal intensity (SI) (r = 0.35). Native SI was inversely correlated with PD-L1 (r = -0.32). Difference in SI between the transitional and portal phase correlated with glypican-3 expression (r = 0.32). Conclusion: DCE-MRI shows a moderate association with stromal infiltrating lymphocytes (CD3⁺ SIL) in HCC. Associations with other components of the TME, including tumor-infiltrating lymphocytes (CD3⁺ TIL), PD-L1 and Glypican-3 expression, were observed at uncorrected thresholds, but did not remain statistically significant after correction for multiple testing. Key Points: Question DCE-MRI constitutes the cornerstone of HCC diagnosis. Is quantitative assessment of wash-in, wash-out and hepatobiliary uptake associated with non-invasive characterization of the TME? Findings CD3⁺ SIL were associated with tumor wash-in and wash-out parameters. Exploratory associations involving CD3⁺ TIL, PD-L1, and glypican-3 lost significance after multiple-testing adjustment. Relevance statement Quantitative DCE-MRI parameters may provide additional non-invasive information regarding tumor tissue characteristics and the tumor microenvironment of HCC. Graphical Abstract:
SN - 2509-9280
ER -