Expression of the B7-related molecule ICOSL by human glioma cells in vitro and in vivo

TY - JOUR

T1 - Expression of the B7-related molecule ICOSL by human glioma cells in vitro and in vivo

AU - Schreiner, Bettina

AU - Wischhusen, Jörg

AU - Mitsdoerffer, Meike

AU - Schneider, Dagmar

AU - Bornemann, Antje

AU - Melms, Arthur

AU - Tolosa, Eva

AU - Weller, Michael

AU - Wiendl, Heinz

N1 - Copyright 2003 Wiley-Liss, Inc.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antigens, CD

KW - Antineoplastic Agents

KW - Brain Neoplasms

KW - CD8-Positive T-Lymphocytes

KW - Carrier Proteins

KW - Cell Line, Tumor

KW - Cells, Cultured

KW - Coculture Techniques

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Glioblastoma

KW - Humans

KW - Inducible T-Cell Co-Stimulator Ligand

KW - Middle Aged

KW - Proteins

KW - Signal Transduction

KW - Tumor Necrosis Factor-alpha

U2 - 10.1002/glia.10291

DO - 10.1002/glia.10291

M3 - SCORING: Journal article

C2 - 14603470

VL - 44

SP - 296

EP - 301

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 3

ER -