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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Exploring tumor dynamics and responses of prostate cancer to IL-27 based treatment combinations through biodynamic
Shreya Kumar1, Dawith Lim2, Harish Kothandaraman3
1Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, 625 Harrison St, West Lafayette, IN, 47907, USA.
Abstract:
The tumor microenvironment (TME) is a highly dynamic network shaped by immune, vascular, and stromal interactions, further modulated by extracellular factors. The high tumor heterogeneity complicates treatment due to evolving resistance. Biodynamic imaging (BDI), a 3D coherence-gated holography technique, quantifies intracellular motion to assess phenotypic responses to therapy. We applied BDI to prostate cancer (PCa) treated with IL-27-based combinations to evaluate the dynamic responses of immunotherapy. This study is the first to integrate BDI with RNA-seq to correlate physiological changes with gene expression. Using a subcutaneous PCa model, tumors were treated ex vivo with chemotherapy and immunomodulatory agents. BDI enabled capturing motion frequency shifts (0.01-12.5 Hz), while RNA-seq revealed the molecular changes in the tumors. IL-27 showed potential to modulate the immunologically "cold" TME and enhance therapeutic efficacy. This integrative approach offers a novel platform for evaluating combination strategies in PCa and may inform more effective treatment decisions.
Insights
Biodynamic imaging (BDI) assessed prostate cancer (PCa) responses to immunotherapy. This novel approach correlated cellular motion with gene expression, revealing IL-27
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- The tumor microenvironment (TME) is complex, with heterogeneity driving treatment resistance in cancers like prostate cancer (PCa).
- Assessing dynamic phenotypic responses to therapy is crucial for effective treatment strategies.
Purpose of the Study:
- To evaluate dynamic immunotherapy responses in PCa using Biodynamic Imaging (BDI).
- To integrate BDI with RNA-sequencing (RNA-seq) for correlating physiological changes with gene expression.
- To investigate the efficacy of IL-27-based combination therapies in modulating the TME.
Main Methods:
- Applied 3D coherence-gated holography (BDI) to quantify intracellular motion in a PCa model.
- Treated tumors ex vivo with chemotherapy and immunomodulatory agents, including IL-27 combinations.
- Correlated BDI-derived motion frequency shifts (0.01-12.5 Hz) with RNA-seq data.
Main Results:
- BDI successfully captured dynamic cellular responses to therapeutic interventions.
- RNA-seq identified molecular changes associated with treatment, including immune modulation.
- IL-27 demonstrated potential in converting immunologically 'cold' TME to a more responsive state, enhancing efficacy.
Conclusions:
- The integration of BDI and RNA-seq provides a novel platform for evaluating combination therapies in PCa.
- This approach can inform treatment decisions by linking dynamic physiological changes to molecular profiles.
- Biodynamic imaging offers a promising method for assessing treatment response in challenging cancers.
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