Dynamic contrast-enhanced MRI and tumor microenvironment in hepatocellular carcinoma: exploratory analysis of CD3 + TILs, PD-L1, and glypican-3

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.