| Autor: |
Claudia Maletzki, Vivica Freiin Grote, Friederike Kalle, Thoralf Kleitke, Annette Zimpfer, Anne-Sophie Becker, Wendy Bergmann-Ewert, Anika Jonitz-Heincke, Rainer Bader, Brigitte Vollmar, Stephan Hackenberg, Agmal Scherzad, Robert Mlynski, Daniel Strüder |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Death Discovery, Vol 9, Iss 1, Pp 1-11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2058-7716 |
| DOI: |
10.1038/s41420-023-01671-z |
| Popis: |
Abstract High hydrostatic pressure specifically devitalizes cells and tissues without major changes in their molecular structure. Hence, high hydrostatic pressure may enhance the development of whole-cell anti-tumor vaccines, representing tumor heterogeneity and thus (neo-) antigen diversity. Moreover, safe devitalization of tumor-infiltrated supporting tissue may facilitate reimplantation for functional reconstruction. However, precise high hydrostatic pressure thresholds for safe cancer cell killing are unknown. Here, we show that high hydrostatic pressure of at least 315 MPa is necessary to safely devitalize head and neck squamous cell cancer. A pressure of 210 MPa, which has been used frequently in cancer vaccine preparation, resulted in partial devitalization with 27% live cells in flow cytometry and 4% remaining autofluorescence in cell culture after one week. The remaining cells could form vital tumors in the chorioallantoic membrane assay. In contrast, 315 MPa killed all cells in vitro and prevented tumor outgrowth in ovo. The effectiveness of 315 MPa was attributed to the induction of DNA double-strand breaks, independent of apoptosis, autophagy, or methuosis. Furthermore, 315 MPa continued to induce immunogenic cell death. Our results demonstrate that 315 MPa of high hydrostatic pressure induces safe and sustained devitalization of head and neck cancer cells and tissues. Because of the heterogeneity in pressure resistance, we propose our approach as a starting point for determining the precise thresholds for other cancer entities. Further studies on head and neck cancer should focus on immunological co-cultures, combinations of immune checkpoint inhibition, and accurate anatomical reconstruction with pressure-treated autografts. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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