Principle
Chemotactic recruitment of MDSCs
MDSCs migrate toward tumor-derived signals and infiltrate tumor tissues through extracellular matrix barriers. The Transwell system models this process by enabling measurement of directional migration and invasion toward tumor organoids.
Immunosuppressive Function
Process
Generation and Phenotypic Validation of MDSC-like Cells
Functional Validation of Immunosuppressive Activity
Transwell Co-culture Setup
Compound Treatment and Evaluation
Candidate compounds can be introduced into the system to evaluate their effects on MDSC behavior, including both direct cellular responses and changes in migration and infiltration within the co-culture setup.
THP-1
Standardized MDSC-like cells
Immune suppression assay
Drug screening in tumor model
Read out
MDSC immunosuppressive function is assessed through T-cell clustering assays, while trafficking and infiltration are quantitatively measured using imaging-based cell counting and flow cytometry (FACS), providing orthogonal and complementary readouts. The platform demonstrates that tumor organoids contribute to MDSC infiltration dynamics, while MDSC-like cells exhibit robust immunosuppressive activity in co-culture systems.
In drug profiling studies, differential responses are observed across tumor organoids and MDSC-like cells enabling evaluation of cell type–specific effects. Importantly, certain compounds reduce MDSC-mediated immunosuppression, while others modulate MDSC trafficking and infiltration in a concentration-dependent manner, highlighting distinct and complementary therapeutic strategies.Implications for Drug Development
This MDSC-targeted Anticancer Drug Evaluation Platform (Infiltration) enables:
- Mechanism-driven evaluation of MDSC-targeting therapies
- Identification of agents that disrupt immune suppression via trafficking inhibition
- More predictive assessment of drug efficacy in a human, multicellular tumor cont