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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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