A Novel Multicompartment Barrier‐Free Microfluidic Device Reveals the Impact of Extracellular Matrix Stiffening and Temozolomide on Immune‐Tumor Interactions in Glioblastoma

Abstract The immune system plays a crucial role in shaping the glioblastoma tumor microenvironment, characterized by its complexity and dynamic interactions. Understanding the tumor‐immune crosstalk is essential for advancing cancer research and therapeutic development. Here, a novel multicompartment, barrier‐free microfluidic device is presented that overcomes the limitations of existing models by enabling direct tumor‐immune interactions without physical barriers, preserving natural immune cell infiltration. This platform supports the independent and simultaneous culture of tumor and immune cells, replicating the healthy‐tumoral stroma interface, and allows investigating the effect of matrix stiffness and chemotherapy on both populations. The findings reveal that increased collagen concentration promotes tumor invasiveness while impairing immune cell infiltration. Additionally, temozolomide treatment reduces immune cell motility but enhances anti‐tumor immune responses. These insights highlight the critical roles of extracellular matrix mechanics and chemotherapy in tumor progression and immune modulation, establishing this device as a powerful tool for studying glioblastoma‐immune dynamics and evaluating therapeutic strategies.