In vitro combined effects of a triazene compound and interferon-beta on natural immunity against lymphoblastoid cells: studies at effector and target cell level.
It was shown that Dacarbazine and other triazene compounds render murine leukemias highly immunogenic and susceptible to natural immunity (NI). In addition a pilot clinical study revealed that Dacarbazine can be cytotoxic for bone marrow blasts in patients with acute non-lymphoblastic leukemias through a mechanism that could be, at least in part, of immunological origin. However triazenes depress antigen-dependent responses and NI, whereas interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore the complex interaction between triazenes and IFN on NI effector (i.e. NK) lymphocytes and human target lymphoblastoid cells has been investigated. The results show that: (a) IFN increases NK activity and antagonizes the depressive effects of methyl-triazene-benzoic acid (MTBA, an in vitro active triazene compound) on the NK function; (b) a lymphoblastoid cell line exposed to multiple in vitro treatments with MTBA, shows increased growth rate, augmented chemoresistance to MTBA, and higher susceptibility to NI than parental cells; (c) as expected IFN pretreatment down-regulates the susceptibility of lymphoblastoid cells to NK effectors; (d) however a net "therapeutic gain" was found if the overall influence of MTBA+IFN on target and effector cells is considered.
Bonmassar
L
L
Istituto Superiore di Sanità, Rome, Italy.
D'Atri
S
S
Turriziani
M
M
Giuliani
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008780:Methyltransferases / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D014226:Triazenes / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D014226:Triazenes; C053777:1-4-(3-methyltriazeno)benzoic acid; D016899:Interferon-beta; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase