M N Theodoraki1, K Lorenz2, R Lotfi3, D Fürst4, C Tsamadou5, S Jaekle6, J Mytilineos7, C Brunner8, J Theodorakis9, T K Hoffmann1, S Laban1, P J Schuler1. 1. Department of Oto-Rhino-Laryngology, Head and Neck Surgery University Medical Center, Ulm, Germany. Electronic address: marie.nicole.theodorakis@gmail.com. 2. Department of Oto-Rhino-Laryngology, Hospital of German Armed Forces, Ulm, Germany. Electronic address: kai.lorenz@extern.uni-ulm.de. 3. Institute for Transfusion Medicine, University Hospital Ulm, Germany; Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg, Hessen, Germany. Electronic address: r.lotfi@blutspende.de. 4. Institute for Transfusion Medicine, University Hospital Ulm, Germany; Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg, Hessen, Germany. Electronic address: d.fuerst@blutspende.de. 5. Institute for Transfusion Medicine, University Hospital Ulm, Germany; Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg, Hessen, Germany. Electronic address: c.tsamadou@blutspende.de. 6. Department of Oto-Rhino-Laryngology, Head and Neck Surgery University Medical Center, Ulm, Germany. Electronic address: jaekle@uniklinik-ulm.de. 7. Institute for Transfusion Medicine, University Hospital Ulm, Germany; Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg, Hessen, Germany. Electronic address: j.mytilineos@blutspende.de. 8. Department of Oto-Rhino-Laryngology, Head and Neck Surgery University Medical Center, Ulm, Germany. Electronic address: cornelia.brunner@uniklinik-ulm.de. 9. Department of Urology, Geniki Kliniki, Thessaloniki, Greece. Electronic address: j.theodorakis@web.de.
Abstract
BACKGROUND: Photodynamic therapy (PDT) represents a palliative treatment option for a selected group of patients with head and neck squamous cell carcinoma (HNSCC). PDT induces a local inflammatory reaction with the potential to initiate antitumor immune responses. However, the systemic impact on peripheral immune cells has not been described so far. METHODS: HNSCC patients (n=9) were treated with PDT in a palliative setting. All patients had previously undergone several oncologic treatment regimens. Blood samples were taken before, during and after PDT. Age-matched healthy donors served as control group (NC, n=15). The frequency and absolute number of T- and B-lymphocytes, CD4+CD39+ regulatory T-cells (Treg) and NK-cells were measured by 10-color flow cytometry. Serum concentrations of T cell related cytokine panel, including HMGB1, IL-6, IL-10 and perforin were measured by bead array and ELISA. RESULTS: In heavily pretreated HNSCC patients, the number and frequency of Treg and NK-cells were increased as compared to NC. PDT induced a further increase of the frequency of Treg and NK-cells in the peripheral blood. Additionally, the serum concentrations of HMGB1, IL-6 and IL-10 showed a significant elevation after treatment with simultaneously decreased perforin levels. CONCLUSION: Although PDT is a local treatment regimen, a systemic inflammatory response with altered peripheral immune cell populations and cytokine concentrations is visible. The increased Treg and NK cell numbers after PDT support the hypothesis that PDT may successfully be combined with NK cell or T cell activating immune checkpoint modulators in HNSCC patients to improve HNSCC specific immunity.
BACKGROUND: Photodynamic therapy (PDT) represents a palliative treatment option for a selected group of patients with head and neck squamous cell carcinoma (HNSCC). PDT induces a local inflammatory reaction with the potential to initiate antitumor immune responses. However, the systemic impact on peripheral immune cells has not been described so far. METHODS: HNSCC patients (n=9) were treated with PDT in a palliative setting. All patients had previously undergone several oncologic treatment regimens. Blood samples were taken before, during and after PDT. Age-matched healthy donors served as control group (NC, n=15). The frequency and absolute number of T- and B-lymphocytes, CD4+CD39+ regulatory T-cells (Treg) and NK-cells were measured by 10-color flow cytometry. Serum concentrations of T cell related cytokine panel, including HMGB1, IL-6, IL-10 and perforin were measured by bead array and ELISA. RESULTS: In heavily pretreated HNSCC patients, the number and frequency of Treg and NK-cells were increased as compared to NC. PDT induced a further increase of the frequency of Treg and NK-cells in the peripheral blood. Additionally, the serum concentrations of HMGB1, IL-6 and IL-10 showed a significant elevation after treatment with simultaneously decreased perforin levels. CONCLUSION: Although PDT is a local treatment regimen, a systemic inflammatory response with altered peripheral immune cell populations and cytokine concentrations is visible. The increased Treg and NK cell numbers after PDT support the hypothesis that PDT may successfully be combined with NK cell or T cell activating immune checkpoint modulators in HNSCC patients to improve HNSCC specific immunity.
Authors: Marie-Nicole Theodoraki; Saigopalakrishna S Yerneni; Cornelia Brunner; Joannis Theodorakis; Thomas K Hoffmann; Theresa L Whiteside Journal: Oncoscience Date: 2018-04-29
Authors: Daphne Mytilineos; Jasmin Ezić; Adrian von Witzleben; Joannis Mytilineos; Ramin Lotfi; Daniel Fürst; Chrysanthi Tsamadou; Marie-Nicole Theodoraki; Angelika Oster; Gunnar Völkel; Hans A Kestler; Cornelia Brunner; Patrick J Schuler; Johannes Doescher; Thomas K Hoffmann; Simon Laban Journal: Int J Mol Sci Date: 2020-08-20 Impact factor: 5.923
Authors: Ana Catarina S Lobo; Lígia C Gomes-da-Silva; Paulo Rodrigues-Santos; António Cabrita; Manuel Santos-Rosa; Luís G Arnaut Journal: J Clin Med Date: 2019-12-31 Impact factor: 4.241