Skip to main content
NCBI home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1986 Jul;22(3):211–216. doi: 10.1007/BF00200035

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

Edward D Ball 1,✉, Kim E Nichols 1, Olive S Pettengill 1, George D Sorenson 1, Michael W Fanger 1
PMCID: PMC11038883  PMID: 3015408

Abstract

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.

Keywords: Peripheral Blood Mononuclear Cell, Tumor Cell Line, Gamma Interferon, Small Cell Carcinoma, Cell Mediate Cytotoxicity

Footnotes

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

References

  • 1.Abo T, Balch CM. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1) J Immunol. 1981;127:1024. [PubMed] [Google Scholar]
  • 2.Attalah AM, Needy CF, Naguchi PD, Eisberg BL. Enhancement of carcinoembryonic antigen expression by interferon. Int J Cancer. 1979;24:49. doi: 10.1002/ijc.2910240109. [DOI] [PubMed] [Google Scholar]
  • 3.Bergeret M, Gregorie A, Chang C. Protective effect of interferon on target cells exposed to cellular cytotoxicity. Immunology. 1980;40:637. [PMC free article] [PubMed] [Google Scholar]
  • 4.Bunn PA, Linnoila I, Minna JD, Carney D, Gazdar AF. 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. 1985;65:764. [PubMed] [Google Scholar]
  • 5.Catalona WJ, Ratliff TL, McCool RE. Interferon induced by S. aureus protein A augments natural killing and ADCC. Nature. 1981;291:77. doi: 10.1038/291077a0. [DOI] [PubMed] [Google Scholar]
  • 6.Cochran, Cox . Experimental design. 2nd edition. New York: Wiley and Sons; 1957. 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. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med. 1985;161:1135. doi: 10.1084/jem.161.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Fischer DG, Hubbard WJ, Koren HS. Tumor cell killing by freshly isolated peripheral blood monocytes. Cell Immunol. 1981;58:426. doi: 10.1016/0008-8749(81)90235-5. [DOI] [PubMed] [Google Scholar]
  • 9.Fischer DG, Golightly MG, Koren HS. Potentiation of the cytolytic activity of peripheral blood monocytes by lymphokines and interferon. J Immunol. 1983;130:1220. [PubMed] [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. Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A. N Engl J Med. 1984;311:1148. doi: 10.1056/NEJM198411013111803. [DOI] [PubMed] [Google Scholar]
  • 11.Greenberg AH, Shen L, Medley G. 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. 1975;29:719. [PMC free article] [PubMed] [Google Scholar]
  • 12.Hanson M, Kiessling R, Anderson B, Welsh RM. Effect of interferon and interferon inducers on the NK sensitivity of normal mouse thymocytes. J Immunol. 1980;125:2225. [PubMed] [Google Scholar]
  • 13.Herberman RB, Ortaldo JR, Bonnard GD. Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature. 1979;277:221. doi: 10.1038/277221a0. [DOI] [PubMed] [Google Scholar]
  • 14.Herberman RB, Ortaldo JR, Djeu JY, Holden HT, Jett J, Lang NP, Rubinstein M, Pestka S. Role of interferon in regulation of cytotoxicity by natural killer cells and macrophages. Ann NY Acad Sci. 1980;350:63. doi: 10.1111/j.1749-6632.1980.tb20608.x. [DOI] [PubMed] [Google Scholar]
  • 15.Imai K, Ng A, Glassy M, Ferrone S. 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. 1981;127:505. [PubMed] [Google Scholar]
  • 16.Langman R. Natural killer cells. Nature. 1980;286:208. doi: 10.1038/286208a0. [DOI] [PubMed] [Google Scholar]
  • 17.Liao S-K, Kwong PC, Khosravi M, Dent PB. Enhanced expression of melanoma-associated antigens and β2-microglobulin on cultured human melanoma cells by interferon. J Natl Cancer Inst. 1982;68:19. [PubMed] [Google Scholar]
  • 18.Lindahl P, Leary P, Gresser I. Enhancement by interferon of the expression of surface antigens on murine leukemia L1210 cells. Proc Natl Acad Sci USA. 1983;70:2785. doi: 10.1073/pnas.70.10.2785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Maluish AE, Ortaldo JR, Conlon JC, Sherwin SA, Leavitt R, Strong DM, Weirnik P, Oldham RK, Herberman RB. Depression of natural killer cytotoxicity after in vivo administration of recombinant leukocyte interferon. J Immunol. 1983;131:50. [PubMed] [Google Scholar]
  • 20.Mantovani A, Jerrells TR, Dean JH, Herberman RB. Cytolytic and cytostatic activity on tumor cells of circulating human monocytes. Int J Cancer. 1979;23:18. doi: 10.1002/ijc.2910230105. [DOI] [PubMed] [Google Scholar]
  • 21.Mavier P, Edgington TS. Human monocyte mediated tumor cytotoxicity. J Immunol. 1984;132:1980. [PubMed] [Google Scholar]
  • 22.Moore M, White WJ, Potter MR. Modulation of target cell susceptibility to human natural killer cells by interferon. Int J Cancer. 1980;25:565. doi: 10.1002/ijc.2910250504. [DOI] [PubMed] [Google Scholar]
  • 23.Newman RA, Warner JF, Dennert G. NK recognition of target structures: Is the transferrin receptor the NK target structure? J Immunol. 1984;133:1841. [PubMed] [Google Scholar]
  • 24.Pettengill OS, Faulkner CS, Wurster-Hill DH, Maurer LH, Sorenson GD. Isolation and characterization of a hormone producing cell line from human small cell anaplastic carcinoma of the lung. J Natl Cancer Inst. 1977;58:511. doi: 10.1093/jnci/58.3.511. [DOI] [PubMed] [Google Scholar]
  • 25.Pettengill OS, Sorenson GD, Wurster-Hill DH, Curphy TJ, Noll WW, Cate CC, Maurer LH. Isolation and growth characteristics of continuous cell lines from small cell carcinoma of the lung. Cancer. 1980;45:906. doi: 10.1002/1097-0142(19800301)45:5<906::aid-cncr2820450513>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  • 26.Saijo N, Shimizu E, Irimajiri N, Ozaki A, Kimura K, Takizawa T, Niitani H. 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. 1982;102:195. doi: 10.1007/BF00411340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Santoli D, Trinchieri C, Steplewski Z, Koprowski H. HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans. J Immunol. 1976;117:765. [PubMed] [Google Scholar]
  • 28.Sherwin SA, Mayer D, Ochs JJ, et al. Recombinant leukocyte A interferon in advanced breast cancer: Results of a phase II trial. Ann Int Med. 1983;98:598. doi: 10.7326/0003-4819-98-5-598. [DOI] [PubMed] [Google Scholar]
  • 29.Sorenson GD, Pettengill OS, Brink-Johnson T, Cate CC, Maurer LH. Hormone production by cultures of small-cell carcinoma of the lung. Cancer. 1981;47:1289. doi: 10.1002/1097-0142(19810315)47:6<1289::aid-cncr2820470610>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  • 30.Sorenson GD, Bloom SR, Ghatei MA, DelPrete SA, Cate CC, Pettengill OS. Bombesin production by human small cell carcinoma of the lung. Regul Pept. 1982;4:59. doi: 10.1016/0167-0115(82)90095-7. [DOI] [PubMed] [Google Scholar]
  • 31.Stern P, Gridlund M, Orn A, Wigzell H. Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC. Nature. 1980;285:341. doi: 10.1038/285341a0. [DOI] [PubMed] [Google Scholar]
  • 32.Takasigi M, Michey MR, Terasaki PI. Reactivity of lymphocytes from normal persons on cultured tumor cells. Cancer Res. 1973;33:2898. [PubMed] [Google Scholar]
  • 33.Trinchieri G, Santoli D. Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. J Exp Med. 1978;147:1314. doi: 10.1084/jem.147.5.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Trinchieri G, Santoli D, Koprowski H. Spontaneous cell-mediated cytotoxicity in humans: Role of interferon and immunoglobulins. J Immunol. 1978;120:1849. [PubMed] [Google Scholar]
  • 35.Trinchieri G, Granato D, Perussia B. Interferon-induced resistance of fibroblasts to cytolysis by natural killer cells: Specificity and mechanism. J Immunol. 1981;126:335. [PubMed] [Google Scholar]
  • 36.Weigent DA, Langford MP, Fleischmann WR, Stanton GJ. Potentiation of lymphocyte natural killing by mixtures of alpha or beta interferon with recombinant gamma interferon. Infect Immun. 1983;40:35. doi: 10.1128/iai.40.1.35-38.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Welsh RM, Karre K, Hansson M, Kunkel CA, Kiessling RW. Interferon-mediated protection of normal and tumor target cells against lysis by mouse natural killer cells. J Immunol. 1981;126:219. [PubMed] [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) [PubMed]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES