Drug-mediated increase of susceptibility of human lung cancer to NK or LAK effector cells.
Previous studies in murine models have shown that in vivo or in vitro treatment of tumor cells with mutagenic triazene compounds (TZC) lead to the appearance of novel drug-mediated tumor antigens (DMTA) capable of eliciting graft resistance in syngeneic hosts. This phenomenon, defined as 'chemical xenogenization' (CX), could be of potential value for immunochemotherapy of human neoplasias. It was also shown that TZC modulate NK sensitivity of murine tumor cells. Therefore, experiments were conducted to evaluate whether susceptibility of a human lung adenocarcinoma cell line (H125) to natural cytotoxic effectors could be affected by treatment with an in vitro active TZC. The results showed that drug treatment of H125 line leads to heritable increase of susceptibility to NK and LAK cells. Moreover, increased binding between effector and drug-treated target cells was observed. Additional studies on HLA antigens showed that changes in HLA-ABC molecule expression were probably not involved in TZC-induced increase of NK/LAK susceptibility. These results suggest that TZC treatment of a human tumor could result in increased expression of membrane structures recognized by natural cytotoxic effector cells. Further studies are required to explore whether these changes are generated by mutational events correlated with TZC-induced CX of human cancer cells.
Institute of Experimental Medicine, CNR, Rome, Italy.
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D'Atri
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Marini
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Tentori
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Tricarico
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Fuggetta
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Bonmassar
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D014226:Triazenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D006680:HLA Antigens; D014226:Triazenes; C053777:1-4-(3-methyltriazeno)benzoic acid