Modulating tumor mechanics and vascular barriers to enhance chemotherapy efficacy in pancreatic tumors and melanoma

T-cell infiltration, indicating an immunostimulatory TME, after combination therapy. In contrast, melanoma showed stromal remodeling but a broad reduction in both pro- and anti-inflammatory cytokines, suggesting limited immune activation despite matrix remodeling, in response to the triple treatment. Cytokine profiling in untreated PDAC and melanoma tumors revealed tumor-type-specific immune signatures, and machine learning identified tumor stiffness as a shared predictor of therapeutic response. Collectively, ketotifen and sonopermeation combined with chemotherapy improved drug delivery, immune activation and tumor suppression with pronounced effects in fibrotic KPC PDAC, offering a promising strategy to overcome resistance in stroma-rich cancers.