Antiblastic chemotherapy drugs up-modulate interferon-gamma receptor expression on human malignant T cells.
We have previously shown that the contrasting ability of interferon-gamma (IFN-gamma) either to stimulate the proliferation of malignant T cells or to induce their apoptosis is determined by the low and high intensity of IFN-gamma receptor (IFN-gamma R) expression, respectively. High IFN-gamma R expression is a marker for the T cell stress that precedes apoptosis. In this paper, we show that a 12- to 24-h culture of three human malignant T-cell lines displaying distinct differentiation stages (ST4, PF382, and Jurkat) in medium supplemented with four chemotherapy drugs (etoposide, cisplatin, cytarabine, and daunomycin) up-modulates their IFN-gamma R expression followed by their apoptosis after 24-48 h later. Increased IFN-gamma R expression (by at least an order of magnitude) was observed in 30 to 90% of cells during exposure to pharmacologic drug concentrations. Timely combination of chemotherapy drugs with IFN-gamma may thus provide a more effective way of inhibiting the progress of human malignant T cells through synergistic induction of their apoptosis.
Novelli
F
F
CNR-Center for Immunogenetics and Experimental Oncology, University of Turin, Italy.
Allione
A
A
Bernabei
P
P
Rigamonti
L
L
Forni
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*; D000096743:Interferon gamma Receptor
D000970:Antineoplastic Agents; D002945:Cisplatin; D003561:Cytarabine; D003630:Daunorubicin; D005047:Etoposide; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor