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Lysis of small cell carcinoma of the lung tumor cell lines by gamma interferon-activated allogeneic peripheral blood mononuclear cells: abrogation of killing by pretreatment of tumor cells with gamma interferon

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Summary

Interferon has been shown to enhance the ability of nonspecific cytotoxic mononuclear cells to lyse some, but not all, tumor cells. We have examined the effect of recombinant human gamma interferon (rIFNγ) on the cell-mediated cytolysis of tumor target cells derived from continuously cultured lines of small cell carcinoma of the lung (SCCL). Cells from the SCCL lines DMS 44, 53, 79, 92, and 406 were labeled with 51Cr and incubated with normal and rIFNγ-stimulated peripheral blood mononuclear cells for 18 h at 37 °C and tumor cell lysis estimated by measuring 51Cr release. Although cells from certain SCCL lines were good targets for cell mediated cytotoxicity, susceptibility to lysis was heterogenous among the different SCCL lines. DMS 406 and 79 were, on average, maximally lysed, while DMS 44, 53, and 92 showed less susceptibility to lysis by either control or rIFNγ-stimulated effector cells. In addition, although pretreatment with rIFNγ increased the cytolytic capacity of normal peripheral blood mononuclear cells from several different donors, preincubation of the tumor cell lines with rIFNγ resulted in inhibition of cytolysis mediated by both control and IFN-activated effector cells. These findings suggest that although rIFNγ may enhance cell-mediated lysis of SCCL tumor cells, it may also decrease susceptibility to lysis.

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References

  1. Abo T, Balch CM (1981) A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024

    Google Scholar 

  2. Attalah AM, Needy CF, Naguchi PD, Eisberg BL (1979). Enhancement of carcinoembryonic antigen expression by interferon. Int J Cancer 24:49

    Google Scholar 

  3. Bergeret M, Gregorie A, Chang C (1980) Protective effect of interferon on target cells exposed to cellular cytotoxicity. Immunology 40:637

    Google Scholar 

  4. Bunn PA, Linnoila I, Minna JD, Carney D, Gazdar AF (1985) Small cell lung cancer, endocrine cells of the fetal bronchus, and other neuroendocrine cells express the Leu-7 antigenic determinant present in natural killer cells. Blood 65:764

    Google Scholar 

  5. Catalona WJ, Ratliff TL, McCool RE (1981) Interferon induced by S. aureus protein A augments natural killing and ADCC. Nature 291:77

    Google Scholar 

  6. Cochran and Cox (1957) Experimental design, 2nd edition. Wiley and Sons, New York, pp 86–152

    Google Scholar 

  7. Doyle A, Martin WJ, Funa K, Gazdar A, Carney D, Martin SE, Linnoila I, Cuttitta F, Mulshine J, Bunn P, Minna JD (1985) Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med 161:1135

    Google Scholar 

  8. Fischer DG, Hubbard WJ, Koren HS (1981) Tumor cell killing by freshly isolated peripheral blood monocytes. Cell Immunol 58:426

    Google Scholar 

  9. Fischer DG, Golightly MG, Koren HS (1983) Potentiation of the cytolytic activity of peripheral blood monocytes by lymphokines and interferon. J Immunol 130:1220

    Google Scholar 

  10. Foon KA, Sherwin SA, Abrams PG, Longo DL, Fer MF, Stevenson HC, Ochs JJ, Bottino GC, Schoenberger CS, Zeffren J, Jaffe ES, Oldham RK (1984) Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A. N Engl J Med 311:1148

    Google Scholar 

  11. Greenberg AH, Shen L, Medley G (1975) Characteristics of the effector cells mediating cytotoxicity against antibody-coated target cells. I. Phagocytic and non-phagocytic effector cell activity against eryhtrocyte and tumour target cells in a 51Cr release cytotoxicity assay and (125I)IUdR growth inhibition assay. Immunology 29:719

    Google Scholar 

  12. Hanson M, Kiessling R, Anderson B, Welsh RM (1980) Effect of interferon and interferon inducers on the NK sensitivity of normal mouse thymocytes. J Immunol 125:2225

    Google Scholar 

  13. Herberman, RB, Ortaldo JR, Bonnard GD (1979) Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature 277:221

    Google Scholar 

  14. Herberman RB, Ortaldo JR, Djeu JY, Holden HT, Jett J, Lang NP, Rubinstein M, Pestka S (1980) Role of interferon in regulation of cytotoxicity by natural killer cells and macrophages. Ann NY Acad Sci 350:63

    Google Scholar 

  15. Imai K, Ng A, Glassy M, Ferrone S (1981) Differential effect of interferon on the expression of tumor-associated antigens and histocompatibility antigens on human melanoma cells: relationship to susceptibility to immune lysis mediated by monoclonal antibodies. J Immunol 127:505

    Google Scholar 

  16. Langman R (1980) Natural killer cells. Nature 286:208

    Google Scholar 

  17. Liao S-K, Kwong PC, Khosravi M, Dent PB (1982) Enhanced expression of melanoma-associated antigens and β2-microglobulin on cultured human melanoma cells by interferon. J Natl Cancer Inst 68:19

    Google Scholar 

  18. Lindahl P, Leary P, Gresser I (1983) Enhancement by interferon of the expression of surface antigens on murine leukemia L1210 cells. Proc Natl Acad Sci USA 70:2785

    Google Scholar 

  19. Maluish AE, Ortaldo JR, Conlon JC, Sherwin SA, Leavitt R, Strong DM, Weirnik P, Oldham RK, Herberman RB (1983) Depression of natural killer cytotoxicity after in vivo administration of recombinant leukocyte interferon. J Immunol 131:50

    Google Scholar 

  20. Mantovani A, Jerrells TR, Dean JH, Herberman RB (1979) Cytolytic and cytostatic activity on tumor cells of circulating human monocytes. Int J Cancer 23:18

    Google Scholar 

  21. Mavier P, Edgington TS (1984) Human monocyte mediated tumor cytotoxicity. J Immunol 132:1980

    Google Scholar 

  22. Moore M, White WJ, Potter MR (1980) Modulation of target cell susceptibility to human natural killer cells by interferon. Int J Cancer 25:565

    Google Scholar 

  23. Newman RA, Warner JF, Dennert G (1984) NK recognition of target structures: Is the transferrin receptor the NK target structure? J Immunol 133:1841

    Google Scholar 

  24. Pettengill OS, Faulkner CS, Wurster-Hill DH, Maurer LH, Sorenson GD (1977) Isolation and characterization of a hormone producing cell line from human small cell anaplastic carcinoma of the lung. J Natl Cancer Inst 58:511

    Google Scholar 

  25. Pettengill OS, Sorenson GD, Wurster-Hill DH, Curphy TJ, Noll WW, Cate CC, Maurer LH (1980) Isolation and growth characteristics of continuous cell lines from small cell carcinoma of the lung. Cancer 45:906

    Google Scholar 

  26. Saijo N, Shimizu E, Irimajiri N, Ozaki A, Kimura K, Takizawa T, Niitani H (1982) Analysis of natural killer activity and antibody-dependent cellular cytotoxicity in healthy volunteers and in patients with primary lung cancer and metastatic pulmonary tumors. J Cancer Res Clin Oncol 102:195

    Google Scholar 

  27. Santoli D, Trinchieri C, Steplewski Z, Koprowski H (1976) HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans. J Immunol 117:765

    Google Scholar 

  28. Sherwin SA, Mayer D, Ochs JJ et al (1983) Recombinant leukocyte A interferon in advanced breast cancer: Results of a phase II trial. Ann Int Med 98:598

    Google Scholar 

  29. Sorenson GD, Pettengill OS, Brink-Johnson T, Cate CC, Maurer LH (1981) Hormone production by cultures of small-cell carcinoma of the lung. Cancer 47:1289

    Google Scholar 

  30. Sorenson GD, Bloom SR, Ghatei MA, DelPrete SA, Cate CC, Pettengill OS (1982) Bombesin production by human small cell carcinoma of the lung. Regul Pept 4:59

    Google Scholar 

  31. Stern P, Gridlund M, Orn A, Wigzell H (1980) Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC. Nature 285:341

    Google Scholar 

  32. Takasigi M, Michey MR, Terasaki PI (1973) Reactivity of lymphocytes from normal persons on cultured tumor cells. Cancer Res 33:2898

    Google Scholar 

  33. Trinchieri G, Santoli D (1978) Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. J Exp Med 147:1314

    Google Scholar 

  34. Trinchieri G, Santoli D, Koprowski H (1978) Spontaneous cell-mediated cytotoxicity in humans: Role of interferon and immunoglobulins. J Immunol 120:1849

    Google Scholar 

  35. Trinchieri G, Granato D, Perussia B (1981) Interferon-induced resistance of fibroblasts to cytolysis by natural killer cells: Specificity and mechanism. J Immunol 126:335

    Google Scholar 

  36. Weigent DA, Langford MP, Fleischmann WR, Stanton GJ (1983) Potentiation of lymphocyte natural killing by mixtures of alpha or beta interferon with recombinant gamma interferon. Infect Immun 40:35

    Google Scholar 

  37. Welsh RM, Karre K, Hansson M, Kunkel CA, Kiessling RW (1981) Interferon-mediated protection of normal and tumor target cells against lysis by mouse natural killer cells. J Immunol 126:219

    Google Scholar 

  38. Ball ED, Sorenson GD, Pettengill OS (1986) The expression of myeloid and major histocompatibility antigens on small cell carcinoma of the lung cell lines: modulation by immune interferon. Cancer Res (in press)

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Authors and Affiliations

  1. Departments of Medicine, Microbiology, and Pathology, Dartmouth Medical School, 03756, Hanover, N.H., USA

    Edward D. Ball, Kim E. Nichols, Olive S. Pettengill, George D. Sorenson & Michael W. Fanger

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  1. Edward D. Ball
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  2. Kim E. Nichols
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  3. Olive S. Pettengill
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  4. George D. Sorenson
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  5. Michael W. Fanger
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Additional information

This work was supported by Grants CA 37868, CA 31888, CA31918, CA33852, and AI 19053 awarded by the National Cancer Institute and Institute of Allergy and Infectious Diseases, DHHS. Statistical assistance was provided by Therese Stukel, biostatistician at the Norris Cotton Cancer Center, Hanover, H. H. and supported by Grant CA 23108 from the National Cancer Institute

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Ball, E.D., Nichols, K.E., Pettengill, O.S. et al. Lysis of small cell carcinoma of the lung tumor cell lines by gamma interferon-activated allogeneic peripheral blood mononuclear cells: abrogation of killing by pretreatment of tumor cells with gamma interferon. Cancer Immunol Immunother 22, 211–216 (1986). https://doi.org/10.1007/BF00200035

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  • DOI: https://doi.org/10.1007/BF00200035

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