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...

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Bibliographic Details
Published in:Brain pathology (Zurich, Switzerland) Switzerland), 2003-04, Vol.13 (2), p.165-175
Main Authors: Sabri, Farideh, Chiodi, Francesca, Piret, Jean-Pascal, Wei, Cheng-Hong, Major, Eugene, Westermark, Bengt, Masucci, Maria G., Levitsky, Victor
Format: Article
Language:English
Subjects:
Animals
Annexin A5 - metabolism
Apoptosis - immunology
Astrocytoma - immunology
Astrocytoma - metabolism
Astrocytoma - therapy
Brain Neoplasms - immunology
Brain Neoplasms - metabolism
Brain Neoplasms - therapy
Cell Transformation, Viral - immunology
Cells, Cultured
Humans
Lymphocyte Activation - immunology
Lymphokines - immunology
Lymphokines - therapeutic use
Mice
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - secretion
Tumor Cells, Cultured
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Summary: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 lym‐phokines and lymphokine specific blocking antibodies indicate that synergistic activities of tumor necrosis factor (TNF)‐α and interferon (INF)‐γ 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.
ISSN:1015-6305
1750-3639
DOI:10.1111/j.1750-3639.2003.tb00016.x