Exploring tumor dynamics and responses of prostate cancer to IL-27 based treatment combinations through biodynamic imaging and RNA sequencing analyses.

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.