| Title: | Glioblastoma–natural killer cell crosstalk: insights from dynamic spheroid models reveal the importance of secreted cytokines and the CD155 axis |
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| Authors: | ID Habič, Anamarija (Author)
ID Kolenc Milavec, Tina (Author)
ID Žižek, Pia (Author)
ID Kladnik, Špela (Author)
ID Majc, Bernarda (Author)
ID Senjor, Emanuela (Author)
ID Perišić, Milica (Author)
ID Porčnik, Andrej (Author)
ID Prestor, Borut (Author)
ID Švajger, Urban (Author)
ID Novak, Metka (Author)
ID Breznik, Barbara (Author) |
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| Files: |  URL - Source URL, visit https://link.springer.com/article/10.1186/s12964-026-02826-y
 PDF - Presentation file, download (6,86 MB)
MD5: 809180A6D1428F16D102CBF385A09F23
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  NIB - National Institute of Biology
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| Abstract: | 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. |
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| Keywords: | glioblastoma, immunotherapy, dynamic in vitro models, natural killer cells, cytotoxicity, 21 infiltration, cytokines, CD155 |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 30.03.2026 |
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| Year of publishing: | 2026 |
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| Number of pages: | Str. 1-22 |
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| Numbering: | Vol. 24, [article no.] 289 |
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| PID: | 20.500.12556/DiRROS-30005  |
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| UDC: | 577.2 |
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| ISSN on article: | 1478-811X |
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| DOI: | 10.1186/s12964-026-02826-y |
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| COBISS.SI-ID: | 278556675 |
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| Note: | 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;
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| Publication date in DiRROS: | 11.06.2026 |
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| Views: | 64 |
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| Downloads: | 42 |
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