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HCC fibroblast, matrix and vascular support

Explore a well-mixed stromal and vascular tumor subsystem under prescribed drug concentrations and fixed immune context. No spatial-agent or population prediction is implied.

Quantitative calibration of a spatial QSP model identifies fibroblast impact on HCC immunotherapy ↗

PNAS

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Untreated fixed immune context

Constant tissue concentration experiment over70days. Fixed immune and mediator context; no dose-regimen, spatial-agent, virtual-population or published-response prediction.

0–70 day

Scenario details

Untreated fixed immune context

Constant tissue concentration experiment over70days. Fixed immune and mediator context; no dose-regimen, spatial-agent, virtual-population or published-response prediction.

Readouts

Viable tumor · cell
Latent deterministic mechanism readout; not a measured population endpoint.
Vascular capacity · cell
Latent deterministic mechanism readout; not a measured population endpoint.
Caf abundance · cell
Latent deterministic mechanism readout; not a measured population endpoint.
Matrix concentration · nM
Latent deterministic mechanism readout; not a measured population endpoint.
Angiogenic factor · pg/mL
Latent deterministic mechanism readout; not a measured population endpoint.

Study purpose

  • How do the model's key biological readouts change under untreated fixed immune context?

Assumptions

  • Interpret patterns within this model and starting configuration; do not treat them as clinical predictions or treatment recommendations.

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Simulation time
day
day
70 → 168

Time between reported samples.

day

1 change · Variation 1

Biology

Six-state well-mixed tumor, vascular and fibroblast mechanism with fixed immune context; dashed arrows are mathematical influence, not material transport.

Six-state well-mixed tumor, vascular and fibroblast mechanism with fixed immune context; dashed arrows are mathematical influence, not material transport.

Model details

35 parameters · 6 states · 6 equations · 8 derived outputs

Classification & API access
Therapeutic
Nivolumab prescribed-concentration context, Cabozantinib prescribed-concentration context
Modality
Monoclonal antibody
Target
PD-1 / PDCD1, MET, RET, VEGFR2
Disease / scope
Hepatocellular carcinoma
ParameterDefaultUnitDescription
Activated deathactivated_death0.01651/dayActivated death coefficient used by the released system of model equations.
Angiogenic decayangiogenic_decay16.61/dayAngiogenic decay governing first-order loss from the modeled system.
Angiogenic generationangiogenic_generation0.00011pg/cell/dayAngiogenic generation coefficient used by the released system of model equations.
Angiogenic halfangiogenic_half2410pg/mLAngiogenic half coefficient used by the released system of model equations.
Arginase immune halfarginase_immune_half0.42nMArginase immune half coefficient used by the released system of model equations.
Basal lossbasal_loss0.00011/dayBasal loss coefficient used by the released system of model equations.
Cabo concentrationcabo_concentration0nMCabo concentration coefficient used by the released system of model equations.
Cabo growth halfcabo_growth_half6.5nMCabo growth half governing growth in the modeled biological process.
Cabo vascular halfcabo_vascular_half0.035nMCabo vascular half coefficient used by the released system of model equations.
Conversionconversion0.21/dayConversion coefficient used by the released system of model equations.
Conversion halfconversion_half0.07nMConversion half coefficient used by the released system of model equations.
Cytotoxic ratecytotoxic_rate21/dayCytotoxic rate coefficient used by the released system of model equations.
Divisiondivision0.0121/dayDivision coefficient used by the released system of model equations.
Effector tumor scaleeffector_tumor_scale1.2—Effector tumor scale coefficient used by the released system of model equations.
Fibroblast entryfibroblast_entry1000000cell/mL/dayFibroblast entry coefficient used by the released system of model equations.
Fibroblast limitfibroblast_limit1200000cell/mLFibroblast limit coefficient used by the released system of model equations.
Fixed arginasefixed_arginase0.218574nMFixed arginase coefficient used by the released system of model equations.
Fixed checkpoint brakefixed_checkpoint_brake0.9—Fixed checkpoint brake coefficient used by the released system of model equations.
Fixed effectorsfixed_effectors31362.7cellFixed effectors coefficient used by the released system of model equations.
Fixed regulatorsfixed_regulators24240.1cellFixed regulators coefficient used by the released system of model equations.
Fixed tgfbfixed_tgfb0.165343nMFixed tgfb coefficient used by the released system of model equations.
Matrix activatedmatrix_activated0.00000345nmol/cell/dayMatrix activated coefficient used by the released system of model equations.
Matrix ceilingmatrix_ceiling5000000nMMatrix ceiling coefficient used by the released system of model equations.
Matrix decaymatrix_decay0.0351/dayMatrix decay governing first-order loss from the modeled system.
Matrix floormatrix_floor200000nMMatrix floor coefficient used by the released system of model equations.
Matrix immune halfmatrix_immune_half500000nMMatrix immune half coefficient used by the released system of model equations.
Matrix restingmatrix_resting0.00000115nmol/cell/dayMatrix resting coefficient used by the released system of model equations.
Nivolumab affinitynivo_affinity4nMNivolumab affinity coefficient used by the released system of model equations.
Nivolumab concentrationnivo_concentration0nMNivolumab concentration coefficient used by the released system of model equations.
Regulatory scaleregulatory_scale11—Regulatory scale coefficient used by the released system of model equations.
Resting deathresting_death0.01651/dayResting death coefficient used by the released system of model equations.
Support decaysupport_decay0.000081/daySupport decay governing first-order loss from the modeled system.
Support generationsupport_generation7.371/daySupport generation coefficient used by the released system of model equations.
Tgfb immune halftgfb_immune_half0.14nMTgfb immune half coefficient used by the released system of model equations.
Tissue volumetissue_volume14.2107mLTissue volume used to convert modeled amount to concentration in the relevant compartment.

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