Nicolle H Rekers1, Catharina M L Zegers2, Ala Yaromina2, Natasja G Lieuwes2, Rianne Biemans2, Birgit L M G Senden-Gijsbers3, Mario Losen4, Evert J Van Limbergen2, Wilfred T V Germeraad3, Dario Neri5, Ludwig Dubois2, Philippe Lambin2. 1. Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. Electronic address: Nicolle.rekers@maastrichtuniversity.nl. 2. Department of Radiation Oncology (MAASTRO), Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 3. Department of Internal Medicine, Division of Hematology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 4. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, The Netherlands. 5. Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Switzerland.
Abstract
BACKGROUND AND PURPOSE: Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses. MATERIAL AND METHODS: In syngeneic F9 tumour bearing 129/FvHsd mice tumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry. RESULTS: Tumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression. CONCLUSION: An additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression.
BACKGROUND AND PURPOSE: Recently, we have shown that radiotherapy (RT) combined with the immunocytokine L19-IL2 can induce long-lasting antitumour effects, dependent on ED-B expression and infiltration of cytotoxic T cells. On the other hand, in certain tumours, IL2 treatment can trigger a natural killer cell (NK) immune response. The aim of this study is to investigate the therapeutic effect of our combination therapy in the ED-B positive F9 teratocarcinoma model, lacking MHCI expression and known to be dependent on NK immune responses. MATERIAL AND METHODS: In syngeneic F9 tumour bearing 129/FvHsd micetumour growth delay was evaluated after local tumour irradiation (10Gy) combined with systemic administration of L19-IL2. Immunological responses were investigated using flow cytometry. RESULTS:Tumour growth delay of L19-IL2 can be further improved by a single dose of RT administered before immunotherapy, but not during immunotherapy. Furthermore, treatment of L19-IL2 favours a NK response and lacks cytotoxic T cell tumour infiltrating immune cells, which may be explained by the absence of MHCI expression. CONCLUSION: An additive effect can be detected when the NK dependent F9 tumour model is treated with radiotherapy and L19-IL2 and therefore this combination could be useful in the absence of tumoural MHCI expression.
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