Antiestrogens sensitize human ovarian and lung carcinomas for lysis by autologous killer cells.
BACKGROUND
The antiestrogens tamoxifen (TX) and toremifene (TO) were shown previously to enhance the lysis of target cells by natural killer cells (NK), lymphokine activated killer (LAK) cells, and by cytotoxic T lymphocytes (CTL).


METHODS
CTL were cultured from lung cancer tissue and from ascites fluid of ovarian carcinoma patients with the aid of human recombinant interleukin-2 (hrIL-2). The target, effector or both cell populations were pretreated by TX, TO and/or with human recombinant interferon-alpha (IFN-alpha).


RESULTS
Significant enhancement of cytotoxicity occurred when the tumor targets or both the target and effector cells were treated with TX, TO or when these drugs were used in combination with IFN-alpha. The lytic activity of CTL cultured from draining lymph nodes of lung cancer patients, was also observed after similar treatment. The lytic effect of autologous LAK cells derived from peripheral blood was increased to a lesser extent, which could be amplified by additional treatment with IFN-alpha.


CONCLUSIONS
The antiestrogens TX and TO and IFN-alpha enhance the lysis of autologous tumor cells by CTL and LAK effectors.
Manitoba Cancer Treatment and Research Foundation, Winnipeg, Canada.
E
E
Baral
E
E
Nagy
G V
GV
Krepart
R J
RJ
Lotocki
H W
HW
Unruh
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I
Berczi
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001201:Ascites / Q000473:pathology; D002277:Carcinoma / Q000473:pathology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013629:Tamoxifen / Q000494:pharmacology*; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D018931:Antineoplastic Agents, Hormonal; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D017312:Toremifene