Method Profile
Measure short-term drug responses in tissue-derived HCC spheroids retaining endogenous immune cells under defined supportive culture conditions.
Explore checkpoint/targeted-drug response and associations with selected animal and clinical outcomes.
40–100 μm multicellular HCC tissue spheroids pooled from five tumor regions in collagen microfluidic culture.
IL-2 and CD3/CD28 support; approximately seven-day immune window; live/dead fluorescence and OKI = 1 − (treated viability/control viability).
Model components
Fresh surgical HCC fragments, collagen, microfluidic device and native tumor/immune populations.
Measurements
AO/PI viability, flow cytometry, immunostaining, whole-exome/RNA sequencing and cytokine assays.
The characterization, matched-PDX and adjuvant cohorts are analyzed separately. Measured OKI is distinct from transcriptome-derived OGI and external-regimen associations.
Characterize culture fidelity, compare selected TKI with matched PDX, and relate adjuvant-regimen OKI to recurrence.
28/30 cultures met viability criterion; longitudinal immune analysis n = 3; selected PDX comparison 10 cases; adjuvant cohort 24.
Parent tissue/day 0, matched vehicle/IgG and immune-free models; selected drug versus PDX control; cohort median OKI groups.
Selected drug produced PDX regression 8/10. Recurrence 12/12 in OKI-low versus 5/12 in OKI-high; OGI external associations were retrospective.
Patient-derived HCC tissue spheroids preserved selected immune components for about seven days. Drug-response comparisons with xenografts and postoperative outcomes supported further study, while a transcriptomic surrogate showed retrospective associations across a different treatment cohort.
