Brach Julia Kristin, Freiin Grote Vivica, Strüder Daniel, Kalle Friederike, Jonitz-Heincke Anika, Bader Rainer, Hoffmann Marco, Scherzad Agmal, Wirth Markus, Hackenberg Stephan
Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital RWTH Aachen, Aachen, Germany.
Center for Integrated Oncology (CIO), University Hospital RWTH Aachen, Aachen, Germany.
Front Immunol. 2025 Jul 28;16:1581014. doi: 10.3389/fimmu.2025.1581014. eCollection 2025.
The devitalization of tissue using high hydrostatic pressure (HHP) is an advanced method for processing tumor-infiltrated cartilage to treat tissue defects. This approach preserves the structural and biomechanical properties of the graft while effectively eliminating tumor cells. However, HHP induces the release of cytokines, which may influence the behavior of residual tumor cells in the surrounding tissue. This study characterizes cytokine profiles of HHP-treated head and neck squamous cell carcinoma (HNSCC) cell lines and evaluated its biological effects on intact tumor cells to further assess the oncological safety of the method.
HHP- treatment resulted in a dose-dependent release of pro-inflammatory cytokines, primarily IL-1α and IL-1β, in all investigated cell lines, while IL-6 and IL-8 concentrations were higher in untreated samples. Functional assays demonstrated that supernatants from HHP-treated HNSCC cells significantly enhanced proliferation, migration, and invasion of HNSCC cells relative to control conditions, with these effects being most pronounced at 200 MPa, a pressure associated with incomplete tumor cell devitalization. At 300 MPa, HHP achieved complete devitalization, correlating with intensified necrotic processes and increased intracellular cytokine release.
Our findings indicate that while HHP significantly influences the cytokine profile and tumor cell behavior, pressures of ≥300 MPa ensure complete tumor cell devitalization, supporting its oncological safety for clinical applications. Further studies are needed to validate these observations and confirm the clinical safety of HHP-treated materials.
利用高静水压(HHP)使组织失活是一种用于处理肿瘤浸润软骨以治疗组织缺损的先进方法。这种方法在有效消除肿瘤细胞的同时,保留了移植物的结构和生物力学特性。然而,HHP会诱导细胞因子的释放,这可能会影响周围组织中残留肿瘤细胞的行为。本研究对经HHP处理的头颈部鳞状细胞癌(HNSCC)细胞系的细胞因子谱进行了表征,并评估了其对完整肿瘤细胞的生物学效应,以进一步评估该方法的肿瘤学安全性。
在所有研究的细胞系中,HHP处理均导致促炎细胞因子呈剂量依赖性释放,主要是IL-1α和IL-1β,而未处理样品中的IL-6和IL-8浓度更高。功能分析表明,与对照条件相比,经HHP处理的HNSCC细胞的上清液显著增强了HNSCC细胞的增殖、迁移和侵袭,在200MPa时这些效应最为明显,该压力与肿瘤细胞不完全失活有关。在300MPa时,HHP实现了完全失活,这与坏死过程加剧和细胞内细胞因子释放增加相关。
我们的研究结果表明,虽然HHP显著影响细胞因子谱和肿瘤细胞行为,但≥300MPa的压力可确保肿瘤细胞完全失活,支持其在临床应用中的肿瘤学安全性。需要进一步的研究来验证这些观察结果,并确认经HHP处理材料的临床安全性。