Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model |
| |
| Authors: | Amer N Kalaaji Jun Lu Svetomir N Markovic Esteban Celis Mark R Pittelkow |
| |
| Institution: | 1. Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA;2. Division of Hematology, Mayo Clinic, Rochester, MN, USA;3. Department of Immunology, Mayo Clinic, Rochester, MN, USA;4. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA;1. Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pa;2. Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, Pa;3. Department of Microbiology & Immunology, Cornell University, Ithaca, NY;4. Department of Veterinary & Biomedical Sciences, Pennsylvania State University, University Park, Pa;5. Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pa;1. Urology Unit, Magna Graecia University of Catanzaro, Catanzaro, Italy;2. La Sapienza University, Department of Urology, Sant'' Andrea Hospital, Rome, Italy;1. Sidney Kimmel Comprehensive Cancer Center, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA;2. Sandra and Edward Meyer Cancer Center, Department of Urology, Weill Cornell Medical College, New York, NY, USA;1. Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA;2. College of Agriculture and Life Sciences, University of Florida, Gainesville, FL 32611, USA;3. Department of Experimental Immunology, Academic Medical Center, Amsterdam, 1105 the Netherlands;4. DNAtrix, Inc., Houston, TX 77021, USA;5. Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, 0313 Oslo, Norway;6. KG Jebsen Centre for Influenza Vaccine Research, University of Oslo, 0313 Oslo, Norway;7. Department of Medicine, University of Florida, Gainesville, FL 32611, USA;1. Urology section, Department of Surgery, University of Catania, Catania, Italy;2. Department of G. F. Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, Italy;3. Department of Urology, Eberhard-Karls-University of Tübingen, Tübingen, Germany |
| |
| Abstract: | Various cytokines, including interferon α (IFNα), tumor necrosis factor α (TNFα), and granulocyte–macrophage colony-stimulating factor (GM-CSF), have been used as adjuvant therapy for advanced-stage melanoma with some success but with marked toxicity, which appears to be related to higher doses. We investigated the efficacy of IFNα, GM-CSF, and TNFα in various combinations to induce antitumor and immune responses in a B16F10 murine melanoma model. These studies showed that GM-CSF, IFNα, and TNFα, when injected together intratumorally, mediated significant inhibition of tumor growth. Tumor regression correlated with local tumor necrosis and significant infiltration of T cells. In addition, this injected intralesional cytokine cocktail also induced lymphadenopathy, with an increase in both CD4+ and CD8+ T cells in the draining lymph nodes. Furthermore, tumor-specific CD8+ T cells were identified from draining lymph nodes. These investigations identify the combined effects of IFNα, GM-CSF, and TNFα in induction of the adaptive immune response and generation of antigen-specific T-cell reactivity. These results support potential clinical trials of the low-dose cytokine combination as adjuvant therapy for melanoma. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
