title: Immunizations with unmodified tumor cells and simultaneous COX-2 inhibition eradicate malignant rat brain tumors and induce a long-lasting CD8(+) T cell memory.
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.
authors.affiliation: Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden; Lund Stem Cell Center, BMC B10, Lund University, SE-221 84 Lund, Sweden. Electronic address: sofia.eberstal@med.lu.se.
authors.forename: Sofia
authors.initials: S
authors.lastname: Eberstål
authors.affiliation: Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Fritzell
authors.affiliation: Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Sandén
authors.affiliation: Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.
authors.forename: Edward
authors.initials: E
authors.lastname: Visse
authors.affiliation: Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Darabi
authors.affiliation: Glioma Immunotherapy Group, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Barngatan 2B, SE-221 85 Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Siesjö
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007371:Interferon-gamma
keywords: CD8(+) T cells; COX-2 inhibition; Immunological memory; Immunotherapy; Malignant brain tumors