Study patient-specific checkpoint responses and associated T-cell and cytokine changes.
Model & Design
Head and neck squamous cell carcinoma organoids with autologous PBMCs; allogeneic immune cells supplied a separate comparison.
Experimental Format
An initial priming/expansion phase followed by a three-day checkpoint effector assay with organoid viability, flow cytometry and cytokines.
Model Components
Component
Tumor material
Description
Fresh and biobanked HNSCC specimens; 28 of 38 specimens generated viable organoids.
Component
Immune cells
Description
Patient blood-derived PBMCs and a limited healthy-donor comparator.
Component
Treatments
Description
Nivolumab, pembrolizumab, relatlimab and nivolumab–relatlimab.
Measurements & Endpoints
Change in Calcein-associated organoid viability
T-cell expansion and phenotype
Secreted IL-17A, Fas ligand and other mediators
Analysis
Use the study-defined 20% viability-reduction threshold while keeping the evaluable subsets for viability, immune phenotyping and clinical observations separate.
Published Evidence
Study Design
Patient-matched tumor–immune response comparisons with exploratory clinical associations.
Study Sample
35 patients supplied 38 specimens; checkpoint viability was evaluable in 11 cases.
Comparison
Checkpoint treatments versus corresponding cocultures, with autologous/allogeneic immune comparisons.
Finding
Checkpoint sensitivity varied; combined blockade did not consistently overcome resistance, while IL-17A associated with functional response.
Interpretation & Limits
The assay lacks several tumor-resident immune populations.
Small retrospective clinical comparisons and cytokine associations are not a validated predictive biomarker test.
Head and neck cancer organoids were paired with blood-derived immune cells to compare PD-1 and LAG-3 blockade. Responses varied by patient, and combined blockade did not consistently overcome resistance.