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Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity

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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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Authors and Affiliations

  1. Department of Immunology, Karolinska Institute, Stockholm, Sweden

    H. Naganuma, M. Hansson & R. Kiessling

  2. Department of Pathology, Karolinska Hospital, Stockholm, Sweden

    S. Venkateswaran

  3. Department of Oncology(Radiumhemmet), Stockholm, Sweden

    G. Masucci, P. WersÄll, C. Hising & H. Mellstedt

  4. Department of Immunology, Karolinska Institute, Box60400, S-10401, Stockholm, Sweden

    E. Halapi

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  1. H. Naganuma
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  4. M. Hansson
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  5. P. WersÄll
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  8. H. Mellstedt
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  9. R. Kiessling
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Naganuma, H., Halapi, E., Masucci, G. et al. Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity. Med Oncol. & Tumor Pharmacother. 9, 25–33 (1992). https://doi.org/10.1007/BF02989650

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