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Natural killer cells have a synergistic anti-tumor effect in combination with chemoradiotherapy against head and neck cancer
Institution:1. Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, South Korea;2. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea;3. Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, South Korea;4. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;5. Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, South Korea;6. Department of Biomedical Science, Chonnam National University Graduate School, Gwangju, South Korea;1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China;2. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China;1. HSC Processing and Cell Therapy Unit, Blood and Tissue Bank of Cantabria, Marqués de Valdecilla Foundation, Hospital de la Santa Cruz de Liencres, Liencres Cantabria, Spain;2. Haematologic Neoplasms and Haematopoietic Stem Cells Transplantation Group, Marqués de Valdecilla Research Institute, Santander, Spain;1. Murdoch Children''s Research Institute, Parkville VIC, Australia;2. The Royal Children''s Hospital, Parkville VIC, Australia;3. The University of Melbourne, Parkville VIC, Australia;4. Cerebral Palsy Alliance Research Institute, University of Sydney, Camperdown NSW, Australia;5. Monash Children''s Hospital, Clayton VIC, Australia;6. Monash University, Clayton VIC, Australia;7. The Children''s Hospital at Westmead, Westmead NSW, Australia;8. Queensland Children''s Hospital, South Brisbane QLD, Australia;9. The University of Queensland, Herston QLD, Australia;10. Royal Brisbane and Women''s Hospitals, Herston QLD, Australia;11. Starship Children''s Hospital, Auckland, New Zealand;12. University of Auckland, Auckland, New Zealand;1. Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, Florida, USA;2. Department of Pathology and Laboratory Medicine, Phoenix Children''s Hospital, Phoenix, Arizona, USA;3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA;4. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri, USA;5. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA;6. Department of Pathology and Laboratory Medicine, University of Miami, Miami, Florida, USA;7. Department of Pathology, Molecular and Cell-Based Medicine, Mount Sinai Health System, Icahn School of Medicine, New York, New York, USA;8. Laboratory Medicine and Pathology and Center for Regenerative Medicine, Mayo Clinic, Jacksonville, Florida, USA;9. Department of Pediatric Hematology/Oncology/Neuro-Oncology/Stem Cell Transplant, Ann & Robert H. Lurie Children''s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA;10. Division of Transfusion Medicine and Cellular Therapy, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA;11. Department of Clinical Hematology and Bone Marrow Transplant, Tata Medical Center, Kolkata, India;12. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA;1. Krembil Research Institute, Toronto, ON, Canada;2. Princess Margaret Cancer Centre, Toronto, ON, Canada;3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada;4. Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Abstract:BackgroundThe use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to augment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC).MethodsNK cells were expanded using our recently established K562-OX40 ligand and membrane-bound interleukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors.ResultsThe results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function–associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1, -2 and -3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC.ConclusionsOur findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.
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