Chemical xenogenization induced by triazene compounds: Changes of susceptibility to NK-mediated cytolysis of human lymphoblastoid cells treated with monomethyl-triazene-benzoic acid

Previous studies showed how in vivo treatment wit]h Dacarbazine or with other triazene compounds renders murine leukemia cells highly immunogenic (i.e. chemical xenogenization' or CX phenomenon) and susceptible to natural immunity [operationally defined as CX concerning natural immunity (NI), i.e. CX (NI)]. Triazenes are profoundly immunodepressant, and interferons, including interferon-beta (IFN), antagonize drug-induced impairment of NI. Therefore, experiments have been performed to study the complex interaction between triazenes and IFN on human target cells in vitro, searching for a possible CX (NI) phenomenon. Natural killer (NK) cells (which represent part of the NI system in vitro) obtained from different donors, were tested against target EBV-immortalized B cells, untreated or treated with MTBA for 2 - 6 transfer generations. The results showed that: (a) four lymphoblastoid cell lines (Xn lines) exposed to multiple treatments in vitro with MTBA gave origin to MTBA-treated sublines (XnMm lines), which were more susceptible (X3Mm), or less suceptible (X1Mm) with respect to parental cells, to NK-mediated cytolysis; (b) treatment of target cells with IFN reduced their suspeptibility to NK effector lymphocytes in X3 and X3Mm, but not in X1 and X1Mm blasts; (c) no difference in the expression of CD19 and CD22 B-cell markers was found between X3 and X3M3 cell lines. However, reduction of these antigens was detected following treatment with IFN. These results could provide rational bases for optimizing immuno-chemotherapy protocols using triazenes and IFN in lymphoma-bearing patients.