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doi:10.22028/D291-33632
Titel: | Collagen density defines 3D migration of CTLs and their consequent cytotoxicity against tumor cells |
VerfasserIn: | Zhao, Renping Zhou, Xiangda Khan, Essak S. Alansary, Dalia Friedmann, Kim S. Yang, Wenjuan Schwarz, Eva C. del Campo Bécares, Aránzazu Hoth, Markus Qu, Bin |
Sprache: | Englisch |
Verlag/Plattform: | bioRxiv |
Erscheinungsjahr: | 2021 |
Dokumenttyp: | Sonstiges |
Abstract: | Solid tumors are often characterized by condensed extracellular matrix (ECM). The impact of dense ECM on cytotoxic T lymphocytes (CTL) function is not fully understood. Here, we report that CTL-mediated cytotoxicity is substantially impaired in dense collagen matrices. Although the intrinsic killing machinery including expression of cytotoxic proteins and degranulation was intact, CTL motility was substantially compromised in dense collagen. We found that for 3D CTL migration, persistence and velocity was regulated by collagen stiffness and the porosity, respectively. Interestingly, 3D CTL velocity is strongly correlated with their nuclear deformability/flexibility during migration, which is regulated by the microtubule network. Moreover, CTL migration was completely abolished by inhibition of actin polymerization and or myosin IIA. Remarkably, disruption of the microtubule-networks significantly improves the impaired migration, search efficiency, and cytotoxicity of CTLs in dense collagen. Our work suggests the microtubule network as a promising target to rescue impaired CTL killing capacity in solid tumor related scenarios. |
DOI der Erstveröffentlichung: | 10.1101/2021.03.16.435689 |
URL der Erstveröffentlichung: | https://www.biorxiv.org/content/10.1101/2021.03.16.435689v1 |
Link zu diesem Datensatz: | hdl:20.500.11880/32123 http://dx.doi.org/10.22028/D291-33632 |
Datum des Eintrags: | 4-Jan-2022 |
Bemerkung/Hinweis: | Preprint |
Fakultät: | M - Medizinische Fakultät NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | M - Biophysik NT - Chemie |
Professur: | M - Prof. Dr. Markus Hoth NT - Prof. Dr. Aránzazu del Campo |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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