Expression of the B7-related molecule ICOSL by human glioma cells in vitro and in vivo.
Human glioblastoma is a highly lethal tumor known for its capability of interfering with effective antitumor immune responses. Costimulatory signals are of critical relevance in both the inductive and effector phases of immune responses. Inducible costimulator-ligand (ICOSL), a member of the B7 family of costimulatory molecules related to CD80/CD86, regulates CD4 as well as CD8 T-cell responses via interaction with its receptor, ICOS, on activated T cells. We report the expression of ICOSL by glioma cells in vitro and in vivo. In contrast to CD80 (B7.1) and CD86 (B7.2), ICOSL protein and mRNA was expressed in 7 of 12 glioma cell lines. ICOSL expression is upregulated by the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), whereas interferon-gamma (IFN-gamma) has no such effect. Further, immunohistochemical analysis of human brain tumors demonstrates the expression of ICOSL in three of four tissue samples. ICOSL expression is functional in that a neutralizing ICOSL antibody (HIL-131) reduces Th1 and Th2 cytokine levels in cocultures of peripheral blood lymphocytes or T-cell subsets (CD4 and CD8) with glioma cells. However, ICOSL gene transfer into glioma cells does not alter their immunogenicity under primary or secondary alloreactive coculture assays.
Schreiner
Bettina
B
Department of Neurology, University of Tübingen, Medical School, Tübingen, Germany.
Wischhusen
Jörg
J
Mitsdoerffer
Meike
M
Schneider
Dagmar
D
Bornemann
Antje
A
Melms
Arthur
A
Tolosa
Eva
E
Weller
Michael
M
Wiendl
Heinz
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000276:immunology* / Q000503:physiopathology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D005909:Glioblastoma / Q000276:immunology* / Q000503:physiopathology*; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D008875:Middle Aged; D011506:Proteins; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D000970:Antineoplastic Agents; D002352:Carrier Proteins; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha