Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters

Area of Science:

• Oncology
• Biotechnology
• Immunology

Background:

• Tumor microenvironment crosstalk between cancer cells, T cells, and myeloid-derived suppressor cells (MDSCs) is crucial for tumor progression and treatment response.
• Existing patient-derived models like organoids and 2D cultures fail to fully capture complex tumor-immune interactions due to missing cell types (e.g., MDSCs).

Purpose of the Study:

• To develop a novel 3D model, acoustically assembled patient-derived cell clusters (APCCs), that preserves original tumor and immune cell compositions.
• To enable rapid, scalable, and user-friendly modeling of 3D tumor-immune interactions and testing of treatment responses.

Main Methods:

• Utilizing 3D acoustic trappings within an extracellular matrix to assemble hundreds of APCCs within minutes.
• Incorporating sensitive, short-lived tumor-induced MDSCs into APCCs to model their dynamic suppression of T cell activity.
• Testing the combined therapeutic effects of a multi-kinase inhibitor (cabozantinib) and an anti-PD-1 immune checkpoint inhibitor (pembrolizumab) using APCCs.

Main Results:

• APCCs successfully preserved original tumor/immune cell compositions and modeled their interactions in a 3D microenvironment.
• The model effectively preserved tumor-induced MDSCs and demonstrated their T cell suppression dynamics.
• Successful modeling of the combinational therapeutic effect of cabozantinib and pembrolizumab.

Conclusions:

• APCCs offer a promising platform for predicting patient treatment responses in personalized cancer adjuvant therapy.
• This novel model can be used for screening novel cancer immunotherapies and combination therapies.
• APCCs provide a rapid, scalable, and user-friendly approach to studying complex tumor-immune interactions.