title: Therapeutical doses of temozolomide do not impair the function of dendritic             cells and CD8+ T cells.
abstract: The median survival of patients with glioblastoma multiforme (GBM) remains poor. Innovative immunotherapies with dendritic cell (DC) vaccination might be combined with standard temozolomide (TMZ) treatment. Here, we evaluated the influence of TMZ on the phenotype and function of DCs and CD8+ T cells. DCs were generated from the peripheral blood of healthy volunteers (HVs) and GBM patients. DCs were analyzed by light microscopy and flow cytometry. Phagocytic activity was tested by FITC-dextran engulfment. Mixed lymphocyte peptide cultures were followed by enzyme-linked immunospot (ELISPOT) and flow cytometry assays. TMZ was added to DC and T cell cultures at concentrations up to 500 µM. Mature DCs were generated from HVs and GBM patients. Cells displayed a typical DC morphology and a mature DC phenotype. Expression of CD209 was even higher in DCs generated from patients under therapy than from HVs (75.2 vs. 51.1%). In contrast, CD40 (1.1 vs. 13.5%) and BDCA4 (26.5 vs. 52.9%) were lower expressed in GBM patients at time of diagnosis. Immature DCs showed high phagocytic activity. Addition of TMZ at concentrations up to 50 µM did neither impair the phenotype nor the function of DCs. In ELISPOT and flow cytometry assays, no impairment of CD8+ T cell responses to viral antigens could be observed. Taken together, TMZ does not impair the function of either DCs or the CD8+ T cells.
authors: Department of Immunology, Jiangsu University, Zhenjiang, People's Republic of China.
authors: Xun
authors: X
authors: Xu
authors: Florian
authors: F
authors: Stockhammer
authors: Anita
authors: A
authors: Schmitt
authors: Rosaely
authors: R
authors: Casalegno-Garduno
authors: Anne
authors: A
authors: Enders
authors: Jiju
authors: J
authors: Mani
authors: Carl Friedrich
authors: CF
authors: Classen
authors: Michael
authors: M
authors: Linnebacher
authors: Mathias
authors: M
authors: Freund
authors: Michael
authors: M
authors: Schmitt
mesh_terms: D000368:Aged; D000954:Antigens, Surface / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D000077204:Temozolomide
chemical_list: D000954:Antigens, Surface; D007376:Interleukin-2; C478196:blood dendritic cell antigen 4, human; D003606:Dacarbazine; D000077204:Temozolomide