Soluble factors released by virus specific activated cytotoxic T-lymphocytes induce apoptotic death of astroglioma cell lines.
Astrocytomas and astrogliomas represent the most common types of primary tumors in human central nervous system and are associated with high mortality due to the absence of efficient therapy. Here we demonstrate that, upon antigen-specific activation, cytotoxic T-lymphocytes (CTLs) secrete products that inhibit proliferation and induce apoptosis in a significant proportion of astroglioma cell lines. This effect is tumor specific in that normal cultured astrocytes do not develop apoptotic changes upon exposure to supernatant of activated CTLs. Experiments with purified lymphokines and lymphokine specific blocking antibodies indicate that synergistic activities of tumor necrosis factor (TNF)-alpha and interferon (INF)-gamma are required for the apoptosis inducing effect on some astroglioma cell lines. However, this effect appears to be dependent on additional factors produced by activated CTLs. Our results suggest that local application of factors released by activated CTLs or induction of CTL migration and activation in the tumor site may have a therapeutic effect in patients with astrogliomas.
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Farideh
F
Sabri
Francesca
F
Chiodi
Jean-Pascal
JP
Piret
Cheng-Hong
CH
Wei
Eugene
E
Major
Bengt
B
Westermark
Maria G
MG
Masucci
Victor
V
Levitsky
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001254:Astrocytoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D002472:Cell Transformation, Viral / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D008222:Lymphokines