000149075 001__ 149075
000149075 005__ 20251017144646.0
000149075 0247_ $$2doi$$a10.1016/j.lfs.2024.123335
000149075 0248_ $$2sideral$$a142157
000149075 037__ $$aART-2024-142157
000149075 041__ $$aeng
000149075 100__ $$aZhang-Zhou, Jack$$uUniversidad de Zaragoza
000149075 245__ $$aCAR-T cells are more affected than T lymphocytes by mechanical constraints: A microfluidic-based approach
000149075 260__ $$c2024
000149075 5060_ $$aAccess copy available to the general public$$fUnrestricted
000149075 5203_ $$aAims: CAR-T cell therapy has attracted considerable attention in recent years owing to its well-known efficacy against haematopoietic malignancies. Nevertheless, this immunotherapy fails against solid tumours due to hostile conditions found in the tumour microenvironment. In this context, many relevant biochemical factors have been thoroughly studied, but crucial mechanical cues have been underestimated. Main methods: We developed an innovative approach using microfluidic devices, which recreate the biomechanical aspects of solid tumours. Using these platforms, we quantified immune cell migration (T and CAR-T cells) under different confinement conditions.
Key findings: We found that both CAR-T cell and T cell velocities are affected by the biomechanical and chemical cues studied, which are closely related to those found in solid tumours. Under biochemical stimulus-free conditions, the velocity of T cells is independent of the width of the microchannel, whereas the velocity of CAR-T cells is greatly reduced in the highest confinement channels. When chemoattractants or tumour cells are added, immune cells display increased confined migration velocity. However, in the presence of immunosuppressive chemokines, T cells become slower, whereas CAR-T cells significantly increase their velocity via a chimeric cytokine receptor. Significance: Our approach contributes to a better understanding of immune cell migration and the influence of mechanical constraints, which will allow the testing of new ways to improve CAR-T cell trafficking into solid tumours. Therefore, our study revealed that the migratory behaviour of CAR-T cells differs from that of T cells under confined conditions and that biomechanical cues, such as cell deformability caused by confinement, can influence the correct infiltration of immune cells into solid tumours during the immune response.
000149075 536__ $$9info:eu-repo/grantAgreement/ES/AEI/FJC2021-048046-I$$9info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS$$9info:eu-repo/grantAgreement/ES/MEFP/FPU21/06003$$9info:eu-repo/grantAgreement/ES/MICINN/PTA2020-018510-I/AEI/10.13039/501100011033
000149075 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000149075 590__ $$a5.1$$b2024
000149075 592__ $$a1.315$$b2024
000149075 591__ $$aPHARMACOLOGY & PHARMACY$$b44 / 352 = 0.125$$c2024$$dQ1$$eT1
000149075 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2024$$dQ1
000149075 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b44 / 195 = 0.226$$c2024$$dQ1$$eT1
000149075 593__ $$aPharmacology, Toxicology and Pharmaceutics (miscellaneous)$$c2024$$dQ1
000149075 593__ $$aMedicine (miscellaneous)$$c2024$$dQ1
000149075 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000149075 700__ $$0(orcid)0000-0002-0163-8378$$aMovilla Meno, Nieves
000149075 700__ $$aOñate Salafranca, Carmen
000149075 700__ $$0(orcid)0000-0002-1878-8997$$aGomez-Benito, Maria Jose$$uUniversidad de Zaragoza
000149075 700__ $$0(orcid)0000-0003-2612-9235$$aGuerrero, Pedro Enrique$$uUniversidad de Zaragoza
000149075 700__ $$0(orcid)0000-0003-0154-0730$$aPardo Jimeno, Julian$$uUniversidad de Zaragoza
000149075 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía-Aznar, Jose Manuel$$uUniversidad de Zaragoza
000149075 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000149075 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000149075 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000149075 773__ $$g363 (2024), 123335 [12 pp.]$$pLife sci.$$tLIFE SCIENCES$$x0024-3205
000149075 8564_ $$s5223188$$uhttps://zaguan.unizar.es/record/149075/files/texto_completo.pdf$$yVersión publicada
000149075 8564_ $$s2221533$$uhttps://zaguan.unizar.es/record/149075/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000149075 909CO $$ooai:zaguan.unizar.es:149075$$particulos$$pdriver
000149075 951__ $$a2025-10-17-14:33:55
000149075 980__ $$aARTICLE