Abstract
Twenty-two human leukaemias, comprising acute phase leucocytes from 13 acute myeloid and nine lymphoid leukaemias, were tested for susceptibility to spontaneous cell-mediated cytotoxicity (CMC) by untreated lymphocytes and lymphocytes treated for 18 h with 250 IU lymphoblastoid (Namalva) interferon (IFN-α). IFN-amplified killing (IAK) by lymphocytes from 24 normal lymphocyte donors was checked on the K562 erythroleukaemia cell line, for comparison with IAK on fresh leukaemias. Nine leukaemias were tested with lymphocytes from three donors, nine with lymphocytes from six donors, three with lymphocytes from nine donors, and one with lymphocytes from 11 donors. Some degree of susceptibility to IAK was found in five acute myeloid and five lymphoid leukaemias, which was markedly dependent upon the source of the effector lymphocytes and did not correlate with the degree of IAK on K562. The 12 other leukaemias were virtually resistant to IAK. The results emphasize the variability in the capacity of IFN-treated lymphocytes to lyse leukaemias that have not been adapted to tissue culture. The basis of effector recognition of cell line and fresh tumour targets is discussed.
Keywords: Cancer Research, Tissue Culture, Interferon, Acute Phase, Tumour Target
References
- 1.Andersson LC, Nilsson K, Gahmberg CG. K562 — a human erythroleukaemic cell line. Int J Cancer. 1979;23:143. doi: 10.1002/ijc.2910230202. [DOI] [PubMed] [Google Scholar]
- 2.Bakacs T, Gergely P, Klein E. Characterization of cytotoxic human lymphocyte subpopulations. The role of Fc-receptor carrying cells. Cell Immunol. 1977;32:317. doi: 10.1016/0008-8749(77)90208-8. [DOI] [PubMed] [Google Scholar]
- 3.Dennert G, Yogeeswaren G, Yamagata S. Cloned cell lines with natural killer activity. Specificity, function and cell surface markers. J Exp Med. 1981;153:545. doi: 10.1084/jem.153.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Gidlund M, Orn A, Pattengale PK, Jansson M, Wigzell H, Nilsson K. Natural killer cells kill tumour cells at a given stage of differentiation. Nature. 1981;292:848. doi: 10.1038/292848a0. [DOI] [PubMed] [Google Scholar]
- 5.Hansson M, Kiessling R, Andersson B, Kärre K, Roder J. NK cell-sensitive T cell subpopulation in thymus: Inverse correlation to host NK activity. Nature. 1979;278:174. doi: 10.1038/278174a0. [DOI] [PubMed] [Google Scholar]
- 6.Herberman RB, Holden HT. Natural cell-mediated immunity. Adv Cancer Res. 1978;27:305. doi: 10.1016/s0065-230x(08)60936-7. [DOI] [PubMed] [Google Scholar]
- 7.Herberman RB, Djeu JY, Kay HD, et al. Natural killer cells: Characteristics and regulation of activity. Immunol Rev. 1979;44:42. doi: 10.1111/j.1600-065x.1979.tb00267.x. [DOI] [PubMed] [Google Scholar]
- 8.Jondal M, Targan S. In vitro induction of cytotoxic effector cells with spontaneous killer cell specificity. J Exp Med. 1978;148:1621. doi: 10.1084/jem.147.6.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Jondal M, Spina C, Targan S. Human spontaneous killer cells selective for tumour-derived target cells. Nature. 1978;272:62. doi: 10.1038/272062a0. [DOI] [PubMed] [Google Scholar]
- 10.Kall MA, Koren HS. Heterogeneity of human natural killer populations. Cell Immunol. 1978;40:58. doi: 10.1016/0008-8749(78)90315-5. [DOI] [PubMed] [Google Scholar]
- 11.Kaplan J, Callewaert DM. Expression of human T-lymphocyte antigens by natural killer cells. J Natl Cancer Inst. 1978;60:961. doi: 10.1093/jnci/60.5.961. [DOI] [PubMed] [Google Scholar]
- 12.Kay HD, Bonnard GD, West WH, Herberman RB. A functional comparison of human Fc-receptor bearing lymphocytes active in natural cytotoxicity and antibody-dependent cellular cytotoxicity. J Immunol. 1977;118:2058. [PubMed] [Google Scholar]
- 13.Klein E, Vanky F. Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumour cells. Cancer Immunol Immunother. 1981;11:183. [Google Scholar]
- 14.Kunkel LA, Welsh RM. Metabolic inhibitors render “resistant” target cells sensitive to natural killer cell-mediated lysis. Int J Cancer. 1981;27:73. doi: 10.1002/ijc.2910270112. [DOI] [PubMed] [Google Scholar]
- 15.Lee SK, Oliver RTD. Autologous leukaemia-specific T cell-mediated lymphocytotoxicity in patients with acute myelogenous leukaemia. J Exp Med. 1978;147:912. doi: 10.1084/jem.147.3.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Leventhal BG, Halterman RH, Rosenberg EB, Herberman RB. Immune reactivity of leukaemia patients to autologous blast cells. Cancer Res. 1972;32:1820. [PubMed] [Google Scholar]
- 17.Lozzio CB, Lozzio BB. Human chronic myelogenous leukaemia cell line with positive Philadelphia chromosome. Blood. 1975;45:321. [PubMed] [Google Scholar]
- 18.Masucci MG, Klein E, Argov S. Disappearance of the NK effect after explanation of lymphocytes and generation of similar nonspecific cytotoxicity correlated to the level of blastogenesis in activated cultures. J Immunol. 1980;124:2458. [PubMed] [Google Scholar]
- 19.Moore M, Potter MR. Enhancement of human natural cell-mediated cytotoxicity by interferon. Br J Cancer. 1980;41:378. doi: 10.1038/bjc.1980.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Moore M, Vose BM. Extravascular natural cytotoxicity in man: Anti-K562 activity of lymph node and tumour infiltrating lymphocytes. Int J Cancer. 1981;27:265. doi: 10.1002/ijc.2910270303. [DOI] [PubMed] [Google Scholar]
- 21.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]
- 22.Oldham RK, Weiner RS, Mathé G, Breard J, Simmler M-C, Carde P, Herberman RB. Cell-mediated immune responsiveness of patients with acute lymphocytic leukaemia in remission. Int J Cancer. 1976;17:326. doi: 10.1002/ijc.2910170308. [DOI] [PubMed] [Google Scholar]
- 23.Ortaldo JR, Oldham RK, Cannon GC, Herberman RB. Specificity of natural cytotoxic reactivity of normal human lymphocytes against a myeloid leukaemia cell line. J Immunol. 1977;59:77. doi: 10.1093/jnci/59.1.77. [DOI] [PubMed] [Google Scholar]
- 24.Potter MR, Moore M. Natural cytotoxic reactivity of human lymphocyte subpopulations. Immunology. 1979;37:187. [PMC free article] [PubMed] [Google Scholar]
- 25.Potter MR, Moore M. In vitro augmentation of human natural cytotoxic activity. Clin Exp Immunol. 1981;44:332. [PMC free article] [PubMed] [Google Scholar]
- 26.Roder JC, Ahrlund-Richter L, Jondal M. Target-effector interactions in the human and murine natural killer system. Specificity and xenogeneic reactivity of the solubilized natural killer-target structure complex and its loss in a somatic cell hybrid. J Exp Med. 1979;150:471. doi: 10.1084/jem.150.3.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Rosenberg EB, Herberman RB, Levine PH, Halterman RH, McCoy JC, Wunderlich JR. Lymphocyte cytotoxicity reactions to leukaemia-associated antigens in identical twins. Int J Cancer. 1972;9:648. doi: 10.1002/ijc.2910090323. [DOI] [PubMed] [Google Scholar]
- 28.Sondel PM, O'Brien C, Porter L, Schlossman SF, Chess L. Cell-mediated destruction of human leukaemic cells by MHC identical lymphocytes: Requirement for a proliferative trigger in vitro. J Immunol. 1976;117:2197. [PubMed] [Google Scholar]
- 29.Taylor GM. In vitro stimulation of cell-mediated cytotoxicity by acute leukaemias. Br J Cancer. 1981;43:157. doi: 10.1038/bjc.1981.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Taylor GM, Harris R, Freeman CB. Cell-mediated cytotoxicity as a result of immunotherapy in patients with acute myeloid leukaemia. Br J Cancer. 1976;33:137. doi: 10.1038/bjc.1976.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Taylor GM, Zuhrie SR, Harris R. Cell-mediated cytotoxicity in relation to active immunotherapy in acute myeloid leukaemia. Cancer Immunol Immunother. 1979;5:263. [Google Scholar]
- 32.Timonen T, Ortaldo JR, Herberman RB. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981;153:569. doi: 10.1084/jem.153.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Trinchieri G, Santoli D. Anti-viral activity induced by culturing lymphocytes with tumour-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med. 1978;147:1314. doi: 10.1084/jem.147.5.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Vanky F, Argov S, Einhorn S, Klein E. The role of alloantigens in natural killing. Allogeneic but not autologous tumour biopsy cells are sensitive for interferon-induced cytotoxicity of human blood lymphocytes. J Exp Med. 1980;251:1151. doi: 10.1084/jem.151.5.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Vose BM, Moore M. Natural cytotoxicity in humans: Susceptibility of freshly isolated tumour cells to lysis. J Natl Cancer Inst. 1980;65:257. [PubMed] [Google Scholar]
- 36.West WH, Cannon GB, Kay HD, Bonnard GD, Herberman RB. Natural cytotoxic reactivity of human lymphocytes against a myeloid cell line: Characterization of effector cells. J Immunol. 1977;48:355. [PubMed] [Google Scholar]
- 37.Zarling JM, Raich PC, McKeough M, Bach FH. Generation of cytotoxic lymphocytes in vitro against autologous human leukaemia cells. Nature. 1976;262:691. doi: 10.1038/262691a0. [DOI] [PubMed] [Google Scholar]
- 38.Zarling JM, Eskra L, Borden EC, Horoszewicz J, Carter WA. Activation of human natural killer cells cytotoxic for human leukaemia cells by purified interferon. J Immunol. 1979;123:63. [PubMed] [Google Scholar]