The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Substrate Rigidity Regulates Human T Cell Activation and Proliferation
Open accessAbstract
Adoptive immunotherapy using cultured T cells holds promise for the treatment of cancer and infectious disease. Ligands immobilized on surfaces fabricated from hard materials such as polystyrene plastic are commonly employed for T cell culture. The mechanical properties of a culture surface can influence the adhesion, proliferation, and differentiation of stem cells and fibroblasts. We therefore explored the impact of culture substrate stiffness on the ex vivo activation and expansion of human T cells. We describe a simple system for the stimulation of the TCR/CD3 complex and the CD28 receptor using substrates with variable rigidity manufactured from poly(dimethylsiloxane), a biocompatible silicone elastomer. We show that softer (Young’s Modulus [E] < 100 kPa) substrates stimulate an average 4-fold greater IL-2 production and ex vivo proliferation of human CD4+ and CD8+ T cells compared with stiffer substrates (E > 2 MPa). Mixed peripheral blood T cells cultured on the stiffer substrates also demonstrate a trend (nonsignificant) toward a greater proportion of CD62Lneg, effector-differentiated CD4+ and CD8+ T cells. Naive CD4+ T cells expanded on softer substrates yield an average 3-fold greater proportion of IFN-γ–producing Th1-like cells. These results reveal that the rigidity of the substrate used to immobilize T cell stimulatory ligands is an important and previously unrecognized parameter influencing T cell activation, proliferation, and Th differentiation. Substrate rigidity should therefore be a consideration in the development of T cell culture systems as well as when interpreting results of T cell activation based upon solid-phase immobilization of TCR/CD3 and CD28 ligands.
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Cites
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Cited by
Yuan, Z., Li, Y., Zhang, S., Wang, X., Dou, H., Yu, X., Zhang, Z., Yang, S., & Xiao, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01744-8 · Cited by 977
Collagen density regulates the activity of tumor-infiltrating T cells
Kuczek, D. E., Larsen, A. M. H., Thorseth, M.-L., Carretta, M., Kalvisa, A., Siersbæk, M. S., Simões, A. M. C., Roslind, A., Engelholm, L. H., Noessner, E., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0556-6 · Cited by 435
Modulating extracellular matrix stiffness: A strategic approach to boost cancer immunotherapy
Mai, Z., Lin, Y., Lin, P., Zhao, X., & Cui, L. (2024) · Cell Death & Disease · doi:10.1038/s41419-024-06697-4 · Cited by 398
The Role of the Extracellular Matrix in Cancer Stemness
Nallanthighal, S., Heiserman, J. P., & Cheon, D.-J. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00086 · Cited by 344
Targeting the tumor stroma for cancer therapy
Xu, M., Zhang, T., Xia, R., Wei, Y., & Wei, X. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01670-1 · Cited by 319
Metadata
- Authors
- O’Connor, R. S., Hao, X., Shen, K., Bashour, K., Akimova, T., Hancock, W. W., Kam, L. C., & Milone, M. C.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08-01
- Volume
- 189
- Issue
- 3
- Pages
- 1330-1339
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2155493718
- Cited by
- 329
- References
- 49
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- bronze
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- O’Connor, R. S., Hao, X., Shen, K., Bashour, K., Akimova, T., Hancock, W. W., Kam, L. C., & Milone, M. C. (2012). Substrate Rigidity Regulates Human T Cell Activation and Proliferation. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1102757
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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