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December 11, 2025npj Precision Oncology0 citationsOpen Access

Differential implications of tumor endothelial cell and lymphocyte densities in advanced hepatocellular carcinoma patients treated with immunotherapy

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GKGwangil KimBKBeodeul KangJHJung Yong Hong

Key Points

  • This research aims to investigate the correlation between tumor microenvironment profiles and treatment efficacy in hepatocellular carcinoma (HCC) patients.
  • Retrospective analysis of H&E images from 163 patients using AI and deep-learning model.
  • Assessment of tumor endothelial cell and lymphocyte densities in patients treated with immune checkpoint inhibitors.
  • Comparison of progression-free survival between cohorts treated with atezolizumab plus bevacizumab and anti-PD-1 monotherapy.
  • High tumor endothelial cell density correlated with longer progression-free survival in the atezo-bev cohort (HR 0.51, p = 0.037).
  • Inflamed immune phenotype predicted longer progression-free survival after anti-PD-1 monotherapy (HR 0.50, p = 0.042).
  • AI-based profiling demonstrated potential for treatment selection based on tumor microenvironment characteristics.

Abstract

We investigated whether artificial intelligence (AI)-based tumor microenvironment profiling correlates with treatment efficacy in unresectable hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitor (ICI) therapies. Spatial distribution of immune/non-immune cells from pretreatment H p = 0.037) but not in the anti-PD-1 monotherapy cohort (HR 1.02 0.59-1.77; p = 0.935). Conversely, inflamed immune phenotype, characterized by high intratumoral TIL densities, predicted longer PFS after anti-PD-1 monotherapy (HR 0.50 0.25-0.99; p = 0.042) but not after atezo-bev (HR 0.92 0.50-1.69; p = 0.762). Our exploratory analysis using AI/deep-learning model demonstrated high TEC density predicted superior outcomes with atezo-bev, while TIL presence correlated with improved anti-PD-1 monotherapy efficacy in HCC patients, suggesting potential clinical applicability in treatment selection.

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Cite This Study

Kim et al. (2025) studied this question.

synapsesocial.com/papers/69401b0d2d562116f28f7251https://doi.org/10.1038/s41698-025-01207-x
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