Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Digital Spatial Profiling of the Tumor-Immune Microenvironment
2.2. Tumor Cell Culture Assays
2.3. Assessment of Global Methylation (5-hmC) Levels in HGSOC
2.4. Tumor-Derived Secreted Cytokine/Chemokine Profiling in Response to DNMTIs
2.5. Optimization of Patient-Derived Organotypic HGSOC Spheroids (PDOTS) in 3D Microfluidic Devices
2.6. Immunofluorescent Imaging of PDOTS
2.7. Identification of Early Markers of Immune Activation in CD4+ and CD8+ T Cells
2.8. Flow Cytometry of Immune Cells
2.9. Assessment of Therapeutic Efficacy in Syngeneic HGSOC Models
2.10. Statistical Analysis
3. Results
3.1. Digital Spatial Proteomic Profiling of Patient TILs in HGSOC
3.2. Epigenetic Priming Reverses Loss of 5-hmC and Mediates Upregulation of Key Tumor Cytokines
3.3. Optimization of Patient-Derived 3D Ex Vivo Platforms for Rapid Immunotherapeutic Testing of HGSOC Tumors and Ascites
3.4. Epigenetic Priming Potentiates ICB in PDOTS and Upregulates Early Activation Immune T Cell Markers
3.5. Epigenetic Priming Increases Overall Survival by Potentiating ICB in Syngeneic HGSOC Models
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gerton, T.J.; Green, A.; Campisi, M.; Chen, M.; Gjeci, I.; Mahadevan, N.; Lee, C.A.A.; Mishra, R.; Vo, H.V.; Haratani, K.; et al. Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells. Cancers 2023, 15, 4128. https://doi.org/10.3390/cancers15164128
Gerton TJ, Green A, Campisi M, Chen M, Gjeci I, Mahadevan N, Lee CAA, Mishra R, Vo HV, Haratani K, et al. Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells. Cancers. 2023; 15(16):4128. https://doi.org/10.3390/cancers15164128
Chicago/Turabian StyleGerton, Thomas J., Allen Green, Marco Campisi, Minyue Chen, Iliana Gjeci, Navin Mahadevan, Catherine A. A. Lee, Ranjan Mishra, Ha V. Vo, Koji Haratani, and et al. 2023. "Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells" Cancers 15, no. 16: 4128. https://doi.org/10.3390/cancers15164128