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Understanding the tumor\u2010immune crosstalk is essential for advancing cancer research and therapeutic development. Here, a novel multicompartment, barrier\u2010free microfluidic device is presented that overcomes the limitations of existing models by enabling direct tumor\u2010immune 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\u2010tumoral 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\u2010tumor 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\u2010immune dynamics and evaluating therapeutic strategies.<\/jats:p>","DOI":"10.1002\/smll.202409229","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T01:17:36Z","timestamp":1738631856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A Novel Multicompartment Barrier\u2010Free Microfluidic Device Reveals the Impact of Extracellular Matrix Stiffening and Temozolomide on Immune\u2010Tumor Interactions in Glioblastoma"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6786-2041","authenticated-orcid":false,"given":"Clara","family":"Bayona","sequence":"first","affiliation":[{"name":"Tissue Microenvironment (TME) Lab Arag\u00f3n Institute of Engineering Research (I3A) University of Zaragoza  Zaragoza 50018 Spain"},{"name":"Institute for Health Research Arag\u00f3n (IIS Arag\u00f3n)  Zaragoza 50009 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2701-3197","authenticated-orcid":false,"given":"Claudia","family":"Olaizola\u2010Rodrigo","sequence":"additional","affiliation":[{"name":"Tissue Microenvironment (TME) Lab Arag\u00f3n Institute of Engineering Research (I3A) University of Zaragoza  Zaragoza 50018 Spain"},{"name":"BEOnChip S.L.  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