149075 20260217205546.0 doi 10.1016/j.lfs.2024.123335 sideral 142157 ART-2024-142157 eng Zhang-Zhou, Jack Universidad de Zaragoza CAR-T cells are more affected than T lymphocytes by mechanical constraints: A microfluidic-based approach 2024 Access copy available to the general public Unrestricted Aims: CAR-T cell therapy has attracted considerable attention in recent years owing to its well-known efficacy against haematopoietic malignancies. Nevertheless, this immunotherapy fails against solid tumours due to hostile conditions found in the tumour microenvironment. In this context, many relevant biochemical factors have been thoroughly studied, but crucial mechanical cues have been underestimated. Main methods: We developed an innovative approach using microfluidic devices, which recreate the biomechanical aspects of solid tumours. Using these platforms, we quantified immune cell migration (T and CAR-T cells) under different confinement conditions. Key findings: We found that both CAR-T cell and T cell velocities are affected by the biomechanical and chemical cues studied, which are closely related to those found in solid tumours. Under biochemical stimulus-free conditions, the velocity of T cells is independent of the width of the microchannel, whereas the velocity of CAR-T cells is greatly reduced in the highest confinement channels. When chemoattractants or tumour cells are added, immune cells display increased confined migration velocity. However, in the presence of immunosuppressive chemokines, T cells become slower, whereas CAR-T cells significantly increase their velocity via a chimeric cytokine receptor. Significance: Our approach contributes to a better understanding of immune cell migration and the influence of mechanical constraints, which will allow the testing of new ways to improve CAR-T cell trafficking into solid tumours. Therefore, our study revealed that the migratory behaviour of CAR-T cells differs from that of T cells under confined conditions and that biomechanical cues, such as cell deformability caused by confinement, can influence the correct infiltration of immune cells into solid tumours during the immune response. info:eu-repo/grantAgreement/ES/AEI/FJC2021-048046-I info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS info:eu-repo/grantAgreement/ES/MEFP/FPU21/06003 info:eu-repo/grantAgreement/ES/MICINN/PTA2020-018510-I/AEI/10.13039/501100011033 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 5.1 2024 PHARMACOLOGY & PHARMACY 44 / 352 = 0.125 2024 Q1 T1 MEDICINE, RESEARCH & EXPERIMENTAL 44 / 195 = 0.226 2024 Q1 T1 1.315 2024 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2024 Q1 Pharmacology, Toxicology and Pharmaceutics (miscellaneous) 2024 Q1 Medicine (miscellaneous) 2024 Q1 10.9 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Movilla Meno, Nieves (orcid)0000-0002-0163-8378 Oñate Salafranca, Carmen Gomez-Benito, Maria Jose Universidad de Zaragoza (orcid)0000-0002-1878-8997 Guerrero, Pedro Enrique Universidad de Zaragoza (orcid)0000-0003-2612-9235 Pardo Jimeno, Julian Universidad de Zaragoza (orcid)0000-0003-0154-0730 García-Aznar, Jose Manuel Universidad de Zaragoza (orcid)0000-0002-9864-7683 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 363 (2024), 123335 [12 pp.] Life sci. LIFE SCIENCES 0024-3205 5223188 http://zaguan.unizar.es/record/149075/files/texto_completo.pdf Versión publicada 2221533 http://zaguan.unizar.es/record/149075/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:149075 articulos driver 2026-02-17-20:38:26 ARTICLE