000169986 001__ 169986
000169986 005__ 20260316092629.0
000169986 0247_ $$2doi$$a10.1016/j.actbio.2026.01.050
000169986 0248_ $$2sideral$$a148621
000169986 037__ $$aART-2026-148621
000169986 041__ $$aeng
000169986 100__ $$aAlamán-Díez, Pilar
000169986 245__ $$aElevated interstitial fluid pressure promotes spheroid growth and reduces CAR-T therapeutic efficacy in solid tumors
000169986 260__ $$c2026
000169986 5060_ $$aAccess copy available to the general public$$fUnrestricted
000169986 5203_ $$aPancreatic ductal adenocarcinoma (PDAC) is among the deadliest solid tumors and is characterized by aggressive progression, a dense tumor microenvironment (TME), and resistance to conventional therapies. Among the barriers to effective treatments, the presence of elevated interstitial fluid pressure (IFP) may be important for drug penetration and immune cell infiltration. In this work, we present an innovative 3D microfluidic PDAC-on-a-chip that allows the application of IFP in a cell chamber to simulate the TME and evaluate the therapeutic efficacy of CAR-T cells engineered against the receptor EGFR expressed in tumor cells. Elevated IFP was associated with increased tumor spheroid growth, reduced caspase activation and decreased actin remodeling, indicating enhanced tumor resistance. CAR-T cells effectively targeted and eliminated tumor cells in 2D and 3D coculture models under normal pressure conditions. However, under high IFP, CAR-Tmediated cytotoxicity was impaired, indicating that some of the low efficacy of CAR-T cell therapy against solid tumors might be derived from IFP. These results highlight the importance of the mechanoenvironment in limiting the efficacy of current immunotherapies. Our model, which incorporates an IFP component, serves as a realistic preclinical platform for testing antitumor therapies in solid tumors. Statement of Significance: In this work, we present an innovative 3D pancreatic tumor-on-a-chip model that incorporates interstitial fluid pressure (IFP), which is a key mechanical component of solid tumors. Using this platform, we discovered that IFP enhances tumor proliferation whilst diminishing immunotherapy efficacy. This indicates the important role of mechanical pressure in limiting immune cell function in solid tumors. Our model is a valuable preclinical platform for investigating the efficacy of anti-tumor therapies and supports the development of strategies to overcome mechanical resistance and enhance therapy efficacy in solid tumors, such as pancreatic cancer.
000169986 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2024-157582OB-I00$$9info:eu-repo/grantAgreement/ES/DGA/ARAID$$9info:eu-repo/grantAgreement/ES/DGA/B29-23R$$9info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS$$9info:eu-repo/grantAgreement/ES/MCIU/PID2024-155384OB-C21$$9info:eu-repo/grantAgreement/ES/MICINN/PTA2020-018510-I/AEI/10.13039/501100011033$$9info:eu-repo/grantAgreement/ES/NextGenerationEU/INVESTIGO-076-16
000169986 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000169986 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000169986 700__ $$aFerrer-Royo, Silvia
000169986 700__ $$aOñate Salafranca, Carmen
000169986 700__ $$aMartín Compaired, Pablo
000169986 700__ $$aBalsas, Patricia
000169986 700__ $$aPardo, Julián
000169986 700__ $$aGarcía-Aznar, José Manuel
000169986 700__ $$aGonzález-Loyola, Alejandra
000169986 773__ $$g(2026), [13 pp.]$$pActa Biomater.$$tACTA BIOMATERIALIA$$x1742-7061
000169986 8564_ $$s3525288$$uhttps://zaguan.unizar.es/record/169986/files/texto_completo.pdf$$yVersión publicada
000169986 8564_ $$s2557355$$uhttps://zaguan.unizar.es/record/169986/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000169986 909CO $$ooai:zaguan.unizar.es:169986$$particulos$$pdriver
000169986 951__ $$a2026-03-16-08:16:18
000169986 980__ $$aARTICLE