ArticleFrontiers in immunology2021
Targeting the Microtubule-Network Rescues CTL Killing Efficiency in Dense 3D Matrices.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Stiff matrix impairs cytotoxic T lymphocyte function at multiple levels.Science advances · 2026Article
- Immune cells employ intermittent integrin-mediated traction forces for 3D migration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Piezo1 as a mechanical checkpoint in T cell immunotherapy for solid tumors.Frontiers in pharmacology · 2026Review
- Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.Cancer communications (London, England) · 2026Review
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Immune Cell Migration Models Synergize Nuclear Piston, Uropod, and Microenvironment into Hydraulic Cell Engine.bioRxiv : the preprint server for biology · 2025Article
- Biomechanics of the tumor extracellular matrix and regulatory T cells: regulatory mechanisms and potential therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming.Current oncology (Toronto, Ont.) · 2025Review
- Breaking barriers: enhancing CAR-armored T cell therapy for solid tumors through microenvironment remodeling.Frontiers in immunology · 2025Review
- Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy.Cell death & disease · 2024Review
- Imaging actin organisation and dynamics in 3D.Journal of cell science · 2024Article
- FMNL1 and mDia1 promote efficient T cell migration through complex environments via distinct mechanisms.Frontiers in immunology · 2024Article
- Review
- Bioactive Constituents ofInternational journal of molecular sciences · 2023Article
- Folylpolyglutamate synthetase mRNA G-quadruplexes regulate its cell protrusion localization and enhance a cancer cell invasive phenotype upon folate repletion.BMC biology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Efficacy of cytotoxic T lymphocyte (CTL)-based immunotherapy is still unsatisfactory against solid tumors, which are frequently characterized by condensed extracellular matrix. Here, using a unique 3D killing assay, we identify that the killing efficiency of primary human CTLs is substantially impaired in dense collagen matrices. Although the expression of cytotoxic proteins in CTLs remained intact in dense collagen, CTL motility was largely compromised. Using light-sheet microscopy, we found that persistence and velocity of CTL migration was influenced by the stiffness and porosity of the 3D matrix. Notably, 3D CTL velocity was strongly correlated with their nuclear deformability, which was enhanced by disruption of the microtubule network especially in dense matrices. Concomitantly, CTL migration, search efficiency, and killing efficiency in dense collagen were significantly increased in microtubule-perturbed CTLs. In addition, the chemotherapeutically used microtubule inhibitor vinblastine drastically enhanced CTL killing efficiency in dense collagen. Together, our findings suggest targeting the microtubule network as a promising strategy to enhance efficacy of CTL-based immunotherapy against solid tumors, especially stiff solid tumors.
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Registered trials
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