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Naslov:Glioblastoma–natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axis
Avtorji:ID Habič, Anamarija (Avtor)
ID Kolenc Milavec, Tina (Avtor)
ID Žižek, Pia (Avtor)
ID Kladnik, Špela (Avtor)
ID Majc, Bernarda (Avtor)
ID Senjor, Emanuela (Avtor)
ID Perišić, Milica (Avtor)
ID Porčnik, Andrej (Avtor)
ID Prestor, Borut (Avtor)
ID Švajger, Urban (Avtor)
ID Novak, Metka (Avtor)
ID Breznik, Barbara (Avtor)
Datoteke:URL URL - Izvorni URL, za dostop obiščite https://link.springer.com/article/10.1186/s12964-026-02826-y
 
.pdf PDF - Predstavitvena datoteka, prenos (6,86 MB)
MD5: 809180A6D1428F16D102CBF385A09F23
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo NIB - Nacionalni inštitut za biologijo
Povzetek:Glioblastoma (GB) is an aggressive primary brain cancer with poor patient prognosis. Natural killer (NK) cells can recognise and eliminate a range of malignant cells, including GB stem cells, which drive GB recurrence. NK cell-based immunotherapy has emerged as a promising approach for GB treatment, but a better understanding of the complex crosstalk between GB and NK cells is needed, particularly within the immunosuppressive GB tumour microenvironment. In this study, we established a reproducible protocol for the production and dynamic culture of uniformly sized GB spheroids using the Celvivo Clinostar system. Our spheroids recapitulated the heterogeneous structure of GB and expressed ligands for NK cell receptors at levels distinct from those observed in corresponding GB cell lines in standard culture, implicating altered sensitivity of GB cells to NK cells in dynamic 3D cultures. GB-NK cell crosstalk was GB cell type dependent and the ability of NK cells to infiltrate GB did not necessarily correlate with their cytotoxicity against GB cells. Spheroids derived from differentiated GB cells secreted higher levels of immunomodulatory cytokines compared to spheroids from GB stem-like cells, and a prominent increase in the secretion of immune-attracting factors was observed in their co-cultures with NK cells. Finally, the CD155-DNAM1/TIGIT axis was indicated as an important regulator of NK cell cytotoxicity against GB stem-like cells. Collectively, our results highlight important factors in GB-NK cell communication and provide a groundwork for further targeted research as well as therapeutic evaluation of NK cell-based approaches in the established dynamic 3D cultures.
Ključne besede:glioblastoma, immunotherapy, dynamic in vitro models, natural killer cells, cytotoxicity, 21 infiltration, cytokines, CD155
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Datum objave:30.03.2026
Leto izida:2026
Št. strani:Str. 1-22
Številčenje:Vol. 24, [article no.] 289
PID:20.500.12556/DiRROS-30005 Novo okno
UDK:577.2
ISSN pri članku:1478-811X
DOI:10.1186/s12964-026-02826-y Novo okno
COBISS.SI-ID:278556675 Novo okno
Opomba:Soavtorji: Tina Kolenc Milavec, Pia Žižek, Špela Kladnik, Bernarda Majc, Emanuela Senjor, Milica Perišić Nanut, Andrej Porčnik, Borut Prestor, Urban Švajger, Metka Novak, Barbara Breznik; Nasl. z nasl. zaslona; Opis vira z dne 18. 5. 2026;
Datum objave v DiRROS:11.06.2026
Število ogledov:63
Število prenosov:42
Metapodatki:XML DC-XML DC-RDF
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Gradivo je del revije

Naslov:Cell communication and signaling
Skrajšan naslov:Cell commun. signal.
Založnik:BioMed Central
ISSN:1478-811X
COBISS.SI-ID:513859097 Novo okno

Gradivo je financirano iz projekta

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0245-2019
Naslov:Ekotoksiologija, toksikološka genomika in karcinogeneza

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:J3-4504-2022
Naslov:Z vizualizacijo mikrookolja glioblastoma do boljše terapije

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:NC-25002-2025
Naslov:Ciljanje glioblasomskih celic v mikrookolju tumorja s kombinacijo obsevanja in selektivnih inhibitorjev metaloproteaz

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:N3-0394-2025
Naslov:Dinamika organoidov za boj proti terapevtski odpornosti glioblastoma

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:L3-3176-2021
Naslov:Vloga in možna uporaba imunomodulatornih mezenhimskih matičnih celic v zdravljenju bolezni COVID-19

Financer:EC - European Commission
Številka projekta:101079113
Naslov:TWINNING FOR EXCELLENCE TO STRATEGICALLY ADVANCE RESEARCH IN CARCINOGENESIS AND CANCER
Akronim:CutCancer

Financer:EC - European Commission
Številka projekta:101136552
Naslov:SPatial Analysis of Cancer Evolution in the Tumour Immune MicroEnvironment
Akronim:SPACETIME

Financer:EC - European Commission
Številka projekta:101215206
Naslov:UNCAN-CONNECT: Decentralized Collaborative Network for Advancing Cancer Research and Innovation
Akronim:UNCAN-Connect

Financer:UKRI - UK Research and Innovation
Številka projekta:10089709
Naslov:GenomeMET: Metrology for genomic profiling to support early cancer detection and precision medicine

Licence

Licenca:CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
Opis:Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:glioblastom, naravne celice ubijalke, modeli raka


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