ArticleFrontiers in oncology2026
Application of patient-derived organotypic tumor spheroids to guide combination immunotherapy for advanced HCC: a case report.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Background: Predicting response to combination immunotherapy in advanced hepatocellular carcinoma (HCC) remains a challenge. The patient-derived organotypic tumor spheroid (PDOTS) model, which may preserve aspects of the tumor immune microenvironment, represents a potentially promising tool for personalized therapy guidance, but its clinical utility in HCC requires further validation. Case presentation: A PDOTS model was generated from a biopsy of a 64-year-old man with advanced HCC (massive tumor with portal vein thrombus). Drug sensitivity testing(DST) in the model suggested sensitivity (Organoid Killing Index=50%) to the combination of Lenvatinib and Tislelizumab, but not to either agent alone. Based in part on this result, the patient received this combination regimen. After 6 cycles, imaging showed a reduction in tumor size, and serum biomarkers (AFP, PIVKA-II) normalized, achieving a partial response that was sustained for 14 cycles. Discussion: The observed clinical response was concordant with the PDOTS prediction. This case suggests that the PDOTS model may partially recapitulate tumor-immune interactions in HCC, addressing a key limitation of traditional models. Its ability to identify a potentially responsive combination regimen highlights its possible utility in guiding treatment decisions. The main limitation is the single-case nature of this report. Conclusion: This study provides preliminary, hypothesis-generating evidence that the PDOTS model may be associated with treatment response to Lenvatinib plus Tislelizumab in advanced HCC, offering a potential platform for personalized immunotherapy selection. Further prospective studies are warranted to validate its predictive value.
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