Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity |
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Authors: | H Naganuma E Halapi G Masucci M Hansson P WersÄll C Hising S Venkateswaran H Mellstedt R Kiessling |
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Institution: | 1. Department of Immunology, Karolinska Institute, Stockholm, Sweden 2. Department of Immunology, Karolinska Institute, Box60400, S-10401, Stockholm, Sweden 3. Department of Oncology(Radiumhemmet), Stockholm, Sweden 4. Department of Pathology, Karolinska Hospital, Stockholm, Sweden
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Abstract: | (First submitted 15 Nov 1991;accepted 11 December 1991) The effect of IFN-γ and TNF-α treatment of an ovarian carcinoma line on the sensitivity to lysis by specific CTL clones and
non-specific Tumor Associated Lymphocytes (TAL), isolated from the ascites fluid, was analyzed. Thein vitro established TAL line displayed a non-specific lytic activity against the autologous tumor as well as against several allogeneic
tumor lines. Pretreatment with IFN-γ alone, or in combination with TNF-α, rendered the carcinoma line less susceptible to
lysis by the autologous TAL line. Conversely, susceptibility to lysis by tumor specific T cell clones, isolated from the TAL
line, was increased as a result of cytokine pretreatment. Several TCR-α/β+, CD8+ T-cell clones showing a more specific pattern of lysis against the autologous tumor were isolated. Lysis of the autologous
tumor by these clones involved the TCR-α/β via a MHC-class I restricted mechanism dependent on the adhesion molecules ICAM-1
and LFA-3, as inferred from antibody blocking studies. The enhanced sensitivity to specific CTL clones seen after cytokine
treatment may be related to theenhanced expression of ICAM-1 molecules on the ovarian carcinoma. These results have implications
for cytokine based immunotherapy, where IFN-γ may enhance the effects of tumor associated specific CTL while decreasing that
of non-specific effector cells. |
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Keywords: | Ovarian carcinoma T-cell clones Cytokine modulation |
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