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Investigating Cancerous Exosomes' Effects on CD8+ T-Cell IL-2 Production in a 3D Unidirectional Flow Bioreactor Using
Daniel Karami1,2, Akhil Srivastava3,4, Rajagopal Ramesh3,4
1School of Chemical, Biological, and Materials Engineering, University of Oklahoma, Norman, OK 73019, USA.
Journal of Functional Biomaterials
|March 24, 2022
Summary
Cancer exosomes suppress T-cell IL-2 production. A novel flow perfusion system using 3D scaffolds demonstrated that flow conditions significantly alter T-cell and cancer exosome interactions, requiring higher exosome concentrations to suppress immune response.
Area of Science:
- Biomedical Engineering
- Immunology
- Cancer Research
Background:
- Cancer cell-derived exosomes suppress anti-tumor immunity by inhibiting T-cells.
- Understanding T-cell and exosome interactions is crucial for developing cancer immunotherapies.
Purpose of the Study:
- To develop and utilize a real-time, 3D cell/scaffold construct flow perfusion system.
- To investigate the impact of cancer exosomes on CD8+ T-cell IL-2 production under flow conditions.
- To assess the role of RGD-functionalized scaffolds in T-cell immobilization and interaction dynamics.
Main Methods:
- Co-culture of human lung cancer exosomes (H1299, A549) with CD8+ T-cells on 3D-printed RGD-functionalized poly(L-lactic) acid (PLLA) scaffolds in a unidirectional flow bioreactor.
- Assessment of Interleukin-2 (IL-2) production at various T-cell to exosome ratios.
- Evaluation of T-cell attachment to scaffolds with varying RGD densities and T-cell retention under perfusion flow.
Main Results:
- Successful immobilization of CD8+ T-cells onto RGD-functionalized PLLA scaffolds, with attachment density correlating to RGD surface density.
- Cancer exosomes significantly suppressed T-cell IL-2 production, with flow conditions requiring higher exosome concentrations for suppression compared to static conditions.
- Flow perfusion at 0.15 mL/min on 3D scaffolds suppressed IL-2 production at a T-cell to exosome ratio of 1:1000, highlighting the influence of hydrodynamic environment.
Conclusions:
- The developed flow perfusion system provides a novel platform for studying T-cell and cancer exosome interactions in a dynamic microenvironment.
- Hydrodynamic conditions in flow perfusion systems significantly modulate the immunosuppressive effects of cancer exosomes on T-cells.
- Findings emphasize the importance of considering dynamic culture conditions for accurate assessment of immune cell-exosome interactions in cancer research.
