Bioprinted Multicomponent Hydrogel Co-culture Tumor-Immune Model for Assessing and Simulating Tumor-Infiltrated...

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Immunology

Background:

• Tumor immune response involves complex interactions between immune cells and cancer.
• Understanding immune cell infiltration into tumors is crucial for effective cancer therapies.
• Patient-derived organoids (PDOs) and tumor-infiltrated lymphocytes (TILs) offer a relevant model system.

Purpose of the Study:

• To develop a bioprinted model for studying immune cell dynamics within a tumor microenvironment.
• To investigate the migratory patterns and activation of TILs in response to gastric cancer organoids.
• To gain insights into the mechanisms of immune cell infiltration for improved adoptive cell therapies.

Main Methods:

• Bioprinting a dual-region model with PDOs and TILs using an alginate, gelatin, and basement membrane bioink.
• Longitudinal tracking of TIL migration and multiplexed cytokine analysis.
• Assessing TIL activity, degranulation, proteolytic activity, and secretion of key molecules (sFas, sFas-ligand, perforin, granzyme).
• Developing a reaction-advection diffusion model based on TIL migratory profiles.

Main Results:

• The bioprinted model enabled longitudinal study of TIL migration and cytokine release.
• TILs demonstrated activation upon encountering PDOs, confirmed by specific molecular signaling and secretion.
• The developed model distinguished between passive and active TIL migration mechanisms.
• Insights into TILs' ability to breach physical barriers were obtained.

Conclusions:

• The bioprinted model provides a valuable platform for pre-screening immune cell fitness and function.
• Understanding TIL infiltration mechanisms is key for optimizing adoptive cell therapies.
• This approach offers a novel strategy to study immune cell-tumor interactions in a controlled environment.