Tumor organoid-immune cell co-culture systems for precision oncology

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunology

Background:

• Three-dimensional tumor organoids, especially patient-derived organoids (PDOs), accurately mimic tumor characteristics.
• Co-culturing organoids with immune cells allows study of the tumor immune microenvironment (TIME) and personalized immunotherapy.

Purpose of the Study:

• To critically evaluate current methodologies for tumor organoid-immune cell co-culture.
• To benchmark success rates, immune cell persistence, and predictive accuracy of these systems.
• To analyze applications in immunotherapy and identify limitations for clinical translation.

Main Methods:

• Review of established co-culture approaches: reductionist, holistic (tumor slice, air-liquid interface), and organoid-on-a-chip.
• Quantitative benchmarking of system performance and discussion of reproducibility challenges.
• Analysis of applications in immune checkpoint blockade, adoptive cell therapy, and advanced "organoid+" technologies.

Main Results:

• Various co-culture systems reveal mechanisms of antitumor immunity and immune escape.
• Applications include screening for immune checkpoint blockade and adoptive cell therapy (CAR-T, CAR-NK, γδ T cells).
• Emerging technologies like spatial transcriptomics and AI-assisted imaging enhance organoid capabilities.

Conclusions:

• Current tumor organoid-immune cell co-culture systems face limitations: batch variability, loss of heterogeneity, poor vascularization, and lack of systemic immune modeling.
• Overcoming these challenges is crucial for clinical adoption and advancing personalized immunotherapy.
• Ethical, regulatory, and standardization issues also require attention for successful translation.