High hydrostatic pressure devitalization of head and neck cancer with cartilage invasion: Oncological safety and immune response after reimplantation

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Cartilage invasion in laryngeal cancer leads to serious deterioration of the functional outcome by diminishing the efficacy of minimal-invasive surgery, chemo- and radiation therapy. Following partial laryngectomy, which remains the safest curative treatment (enabling organ preservation), patients frequently suffer aspiration and permanent tracheostomy due to loss of cartilage. Therefore, a scaffold of precise shape and superb biocompatibility for the reconstruction is urgently needed. Our previous research showed that high hydrostatic pressure treatment specifically devitalizes cells while preserving the structure and the biomechanics of supporting tissue.Here, we introduce the devitalization of tumor-infiltrated cartilage by means of high hydrostatic pressure to facilitate autologous and orthotopic reimplantation. We will confirm the devitalization of all cancer cells in controlled cytotoxicity assays, while the preservation of the cartilage matrix is verified by light and electron microscopy. Remnants of devitalized cells and growth factors remain in the matrix and may affect cells that revitalize the tissue. We will exclude the transformation of stem cells and the increase of cancer cell proliferation in co-culture with the devitalized tumor. Furthermore, we will examine the immune response to the devitalized tissue: Macrophages and lymphocytes are isolated from patients’ blood and exposed to the respective pressure-treated cancer cells. Finally, we will treat VX2 cancer invading the rabbit auricle cartilage with high hydrostatic pressure. After subcutaneous reimplantation outgrowth of viable cancer will be ruled out. This study represents a step towards real anatomic laryngeal reconstruction by the profound investigation of pressure-treated cartilage autografts. Hence, a future application may improve airway protection and voicing for patients after partial laryngectomy. We anticipate our project to be a starting point for further studies using high hydrostatic pressure to fight different aggressive cancer entities and to develop more efficient cancer immunotherapy.