A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments

Area of Science:

• Oncology
• Biotechnology
• Microfluidics

Background:

• Current in vitro cancer models fail to replicate the complex 3D architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors.
• This limitation hinders advancements in basic cancer research and the development of precision medicine.

Purpose of the Study:

• To develop an innovative, patient-specific lung cancer assembloid (LCA) model.
• To overcome the limitations of existing in vitro models by incorporating TME components.
• To establish a more accurate platform for studying lung cancer and predicting treatment responses.

Main Methods:

• Utilized droplet microfluidic technology with a microinjection strategy for precise sample manipulation.
• Rapidly generated LCAs by encapsulating patient tumor-derived TME cells and lung cancer organoids within microgels.
• Ensured intra-batch consistency in LCA size and cell composition.

Main Results:

• LCAs successfully recapitulated inter- and intratumoral heterogeneity, TME cellular diversity, and the genomic/transcriptomic landscape of parental tumors.
• The LCA model demonstrated reconstruction of cancer-associated fibroblast heterogeneity and TME influence on drug responses, outperforming traditional cancer organoids.
• LCAs accurately predicted patient clinical outcomes.

Conclusions:

• The developed microfluidic method enables precise fabrication of cancer assembloids.
• The LCA model serves as a promising platform for advancing lung cancer research and personalized medicine.
• This model holds potential for predicting individualized patient treatment strategies.