Establishing safe high hydrostatic pressure devitalization thresholds for autologous head and neck cancer vaccination and reconstruction

Cell Death Discovery, vol. 9, pp. 390

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 450 MPa is necessary to safely devitalize head and neck squamous cell cancer. A pressure of 300 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, 450 MPa killed all cells in vitro and prevented tumor outgrowth in ovo. The effectiveness of 450 MPa was attributed to the induction of DNA double-strand breaks, independent of apoptosis, autophagy, or methuosis. Furthermore, 450 MPa continued to induce immunogenic cell death. Our results demonstrate that 450 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.

Authors 14

1. Claudia Maletzki

   Universitätsmedizin Rostock

   Affiliation as printed

   Department of Internal Medicine, Medical Clinic III - Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany

2. Vivica Freiin Grote

   Universitätsmedizin Rostock · University of Rostock

   Affiliation as printed

   Research Laboratory for Biomechanics and Implant Technology, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany

3. Friederike Kalle

   Universitätsmedizin Rostock

   Affiliation as printed

   Department of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, Rostock, Germany

4. Thoralf Kleitke

   Universitätsmedizin Rostock

   Affiliation as printed

   Department of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, Rostock, Germany

5. Annette Zimpfer

   Universitätsmedizin Rostock

   Affiliation as printed

   Institute of Pathology, Rostock University Medical Center, Rostock, Germany

6. Anne‐Sophie Becker

   Universitätsmedizin Rostock

   Affiliation as printed

   Institute of Pathology, Rostock University Medical Center, Rostock, Germany

7. Wendy Bergmann‐Ewert

   Universitätsmedizin Rostock · University of Rostock

   Affiliation as printed

   Core Facility for Cell Sorting and Cell Analysis, University Medical Center Rostock, Rostock, Germany

8. Anika Jonitz‐Heincke

   Universitätsmedizin Rostock · University of Rostock

   Affiliation as printed

   Research Laboratory for Biomechanics and Implant Technology, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany

9. Rainer Bader

   Universitätsmedizin Rostock · University of Rostock

   Affiliation as printed

   Research Laboratory for Biomechanics and Implant Technology, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany

10. Brigitte Vollmar

    Universitätsmedizin Rostock

    Affiliation as printed

    Institute for Experimental Surgery, Rostock University Medical Center, Rostock, Germany

11. Stephan Hackenberg Aachen Department of Otorhinolaryngology—Head and Neck Surgery

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Otorhinolaryngology-Head and Neck Surgery, RWTH Aachen University Hospital, Aachen, Germany

12. Agmal Scherzad

    University of Würzburg

    Affiliation as printed

    Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Wuerzburg, Germany

13. Robert Arndt Mlynski

    Universitätsmedizin Rostock

    Affiliation as printed

    Department of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, Rostock, Germany

14. Daniel Strüder corresponding

    Universitätsmedizin Rostock

    Affiliation as printed

    Department of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, Rostock, Germany. Daniel.strueder@med.uni-rostock.de

    Department of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, Rostock, Germany