Immunizations with unmodified tumor cells and simultaneous COX-2 inhibition eradicate malignant rat brain tumors and induce a long-lasting CD8+ T cell memory

• Published in: Journal of neuroimmunology Vol. 274; no. 1; pp. 161 - 167
• Main Authors: Eberstål, Sofia, Fritzell, Sara, Sandén, Emma, Visse, Edward, Darabi, Anna, Siesjö, Peter
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-09-2014
• Subjects: Allergy and Immunology; Animals; Brain Neoplasms - drug therapy; Brain Neoplasms - immunology; Brain Neoplasms - pathology; CD8+ T cells; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Clinical Medicine; COX-2 inhibition; Cyclooxygenase 2 Inhibitors - pharmacology; Disease Models, Animal; Glioma - drug therapy; Glioma - immunology; Glioma - pathology; Immunization - methods; Immunologic Memory - drug effects; Immunologic Memory - immunology; Immunological memory; Immunotherapy; Interferon-gamma - blood; Interferon-gamma - immunology; Klinisk medicin; Male; Malignant brain tumors; Medical and Health Sciences; Medicin och hälsovetenskap; Neurologi; Neurology; Rats; Rats, Inbred F344; COX-2 inhibition; Immunological memory; CD8 + T cells; Immunotherapy; Malignant brain tumors; CD8+ T cells; CD8(+) T cells
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2014.06.019

Abstract Malignant brain tumors induce pronounced immunosuppression, which diminishes immune responses generated by immunotherapy. Here we report that peripheral immunotherapy, using irradiated unmodified whole tumor cells, and systemic cyclooxygenase-2 inhibition induce cure in glioma-bearing rats (60% cure rate), whereas neither monotherapy was sufficient to cure any animal. Moreover, the combined therapy protected against secondary tumor challenges (89% cure rate) and the secondary immune response was correlated with increased plasma interferon-gamma levels and CD8+ T cells systemically and intratumorally. In conclusion, we demonstrate that cyclooxygenase-2 inhibition is sufficient to render unmodified tumor cells immunogenic in immunotherapy of experimental brain tumors.