Application of patient-derived organotypic tumor spheroids to guide combination immunotherapy for advanced HCC: a...

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.

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.

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.

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.