ArticleJournal for immunotherapy of cancer2026
Patient-derived organotypic tumor spheroids as a functional platform for predicting immunotherapeutic responses and guiding precision treatment for hepatocellular carcinoma.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Application of patient-derived organotypic tumor spheroids to guide combination immunotherapy for advanced HCC: a case report.Frontiers in oncology · 2026Article
- AI-integrated single-cell multi-omics decodes the hepatocellular carcinoma metabolism-immune axis: a new strategy for precision therapeutic targeting.Frontiers in oncology · 2026Review
- Decoding the spatial logic of immune evasion in hepatocellular carcinoma: from single-cell profiling to spatial omics.Frontiers in immunology · 2026Review
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Authors and funding
20 authors.
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Abstract
backgroundHepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While immune checkpoint blockade has revolutionized the treatment of many cancers, responses in HCC remain limited. Robust functional platforms capable of predicting individual responses to immunotherapy are urgently needed. In this study, we developed a patient-derived organotypic tumor spheroid (PDOTS) model that preserves the heterogeneity and immune microenvironment of HCC, enabling rapid and reliable assessment of targeted and immunotherapeutic responses.
methodsTumor tissues from 30 HCC patients were processed using a "Five-Point Clock" sampling method and cultured within a three-dimensional microfluidic chip supplemented with IL-2 and CD3/28 activator to maintain tumor-infiltrating lymphocyte activity. The genomic, immune, and histopathological fidelity of PDOTS relative to parental tumors was evaluated. Drug responses were assessed ex vivo and validated in matched patient-derived xenograft (PDX) models. Transcriptomic profiling was subsequently performed to identify gene signatures associated with treatment sensitivity and to construct a transcriptomic predictive model.
resultsThe PDOTS retained ≥60% viability over 7 days and faithfully maintained the genomic, immune, and histopathological profiles of parental tumors. Functionally, PDOTS exhibited immune-dependent responses to PD-1 blockade and predicted treatment responses with 80% concordance in matched PDX models. Transcriptomic profiling revealed distinct metabolic and immune signatures in sensitive and resistant tumors, which were used to derive the "Organoid Killing Index (OKI)". The OKI gene-derived index, a composite index integrating the enrichment scores of gene signatures associated with the OKI, strongly correlated (
conclusionsThese findings establish PDOTS as an immune-competent ex vivo platform for functional precision oncology and support the integration of functional testing with transcriptomic prediction to guide individualized immunotherapy in HCC.
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