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Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumor cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma

  • Original Papers
  • Clinical Oncology
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Abstract

The causes of down-regulation of cytotoxic immune responses in cancer patients have not been fully evaluated. We previously demonstrated that T-cell-growth-factor-activated peripheral blood lymphocytes (PBL) with the surface phenotype CD8+ CD11b−, from patients with widespread metastasis of gastric carcinoma, inhibited the effector process of lymphokine-activated-killer(LAK)-cell-mediated cytolysis. In this study, we examined suppressor cell activity in freshly prepared PBL from 18 patients with advanced gastric carcinoma, and 10 normal healthy individuals. The suppressor cell activity was assayed by recording whether or not PBL inhibited directly the effector process of LAK cell cytotoxicity. Most of the PBL suspensions from cancer patients showed that they contained a population of cells that can directly inhibit the effector phase of tumor cell lysis of the cytotoxic cells. To analyze further the PBL responsible for the suppression, the cells were passed over a nylon-wool column. Nylon-wool-adherent cells significantly augmented the suppression, while the cells passing through abrogated the suppressive effect. Most nylon-wool-adherent cells from 10 normal healthy controls did not inhibit the cytotoxic reaction. To determine further the suppressor-effector population in nylon-wool-adherent cells, negative-selection studies using CD8-, CD4- or CD11b-coated magnetic beads, and positive-selection studies using CD8- or CD4-coated magnetic beads were performed. Finally the results suggest that the suppressor-effector cells comprise at least two different surface phenotypes: CD8+ T and CD8−CD11b+ cells. The possible role of CD4+ T cells and HLA-DR+ LeuM3+ macrophages as suppressor cells was ruled out in nylon-wood-adherent cells. CD8+ T and possibly CD8−CD11b+ cells apparently suppressed the efferent limb of the antitumor immunity. The selective immune suppression mediated by these cells may partly be concerned with escape mechanisms of gastric carcinoma from the host immune surveillance system.

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Abbreviations

TCGF:

T cell growth factor

PBL:

peripheral blood leucocytes

LAK:

lymphokine-activated killer

NK:

natural killer

CTL:

cytotoxic T lymphocytes

References

  • Aruga A, Yamauchi K Takasaki K, Furukawa T, Hanyu F (1991) Induction of autologous tumor-specific cytotoxic T cells in patients with liver cancer. Characterization and clinical utilization. Int J Cancer 49:19–24

    PubMed  Google Scholar 

  • Bykovskaya SN, Abronina IF, Kupriyanova TA, Buvenik J (1990) Down-regulation of LAK cells-mediated cytotoxicity cancer and aging. Biomed Pharmacother 44:333–338

    PubMed  Google Scholar 

  • Clement LT, Grossi CE, Gartland GL (1984) Morphologic and phenotypic features of the subpopulation of Leu-2+ cells that suppresses B cell differentiation. J Immunol 133:2461–2468

    PubMed  Google Scholar 

  • Ebihara T, Koyama S (1990) Functional and phenotypic characteristics of effusion-associated lymphoid cells cultured in the presence of either recombinant interleukin 2 or T-cell growth factor from malignant pleural and peritoneal effusions in patients with advanced carcinoma. Tohoku J Exp Med 162:49–63

    PubMed  Google Scholar 

  • Ebihara T, Koyama S, Fukao K, Osuga T (1989) Lymphokine-activated suppressor (LAS) cells in patients with gastric carcinoma. Cancer Immunol Immunother 28:218–224

    PubMed  Google Scholar 

  • Ebihara T, Fukao K, Koyama S (1990) Functional and phenotypic characteristics of recombinant interleukin-2 or T-cell growth factor-activated spelenic lymphoid cells from patients with gastric or hepatocellular carcinoma. Cancer 66:923–929

    PubMed  Google Scholar 

  • Ebihara T, Sakai N, Koyama S (1991) Suppression by sorted CD8+CD11b− cells from T-cell growth factor-activated peripheral blood lymphocytes on cytolytic activity against tumour in patients with gastric carcinoma. Eur J Cancer 27:1645–1657

    Google Scholar 

  • Fujii T, Igarashi T, Kishimoto S (1987) Significance of suppressor macrophages from immunosurveillance of tumor-bearing mice. J Natl Cancer Inst 78:509–517

    PubMed  Google Scholar 

  • Fujimoto S, Matsuzawa T, Nakagawa K, Tada T (1978) Cellular interaction between cototoxic and suppressor T cells against syngeneic tumors in the mouse. Cell Immunol 38:373–387

    Google Scholar 

  • Han T (1980) Role of suppressor cells in depression of T-lymphocyte proliferative response in untreated and treated Hodgkin's disease. Cancer 45:2102–2108

    PubMed  Google Scholar 

  • Harada Y, Sakatsume M, Nores GA, Hakomori S, Taniguchi M (1989) Density of GM3 with normal primary structure determines mouse melanoma antigenicity; a new concept of tumor antigen. Jpn J Cancer Res 80:988–992

    PubMed  Google Scholar 

  • Jerrells TR, Dean JH, Richardson GL, McCoy JL, Herberman RB (1978) Role of suppressor cells in depletion of in vitro lymphoproliferative responses of lung cancer and breast cancer patients. J Natl Cancer Inst 61:1001–1009

    PubMed  Google Scholar 

  • Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3:645–649

    PubMed  Google Scholar 

  • Kanof ME, Strober W, James SP (1987) Induction of CD4 suppressor T cells with anti-leu 8 antibody. J Immunol 139:49–54

    PubMed  Google Scholar 

  • Kansas GS, Engelman EG (1987) Phenotypic identification of suppressor-effector, suppressor-amplifier and suppressor-inducer T cells of B cell differentiation in man. Eur J Immunol 17:453–457

    PubMed  Google Scholar 

  • Koyama S (1993) Possible role of suppressor cells in the low effectiveness of adoptive immunotherapy for human tumors. Int Med 32:357–358

    Google Scholar 

  • Koyama S, Fujimoto S, Tada T, Sakita T (1981) Effect of baciluus Calmette-Guérin cell wall skeleton on the induction of the cytotoxic and suppressor T cells against syngeneic tumor in the mouse. Int J Cancer27:829–835

    PubMed  Google Scholar 

  • Koyama S, Yoshioka T, Sakita T, Fujimoto S (1985a) Generation of T cell growth factor(TCGF)-dependent splenic lymphoid cell line with cell-mediated immunosuppressive reactivity against syngeneic murine tumor. Eur J Cancer Clin Oncol 21:257–261

    PubMed  Google Scholar 

  • Koyama S, Fukao K, Fujimoto S (1985b) The generation of interleukin-2-dependent suppressor T-cells from patients with systemic metastasis of gastric carcinoma and phenotypic characterization of the cells defined by monoclonal antibodies. Cancer 56:2437–2445

    PubMed  Google Scholar 

  • Koyama S, Ebihara T, Fukao K, Osuga T (1989) Differential activation of lymphokine-activated killer cells with different surface phenotypes by cultivation with recombinant interleukin 2 or T-cell growth factor in gastric cancer patients. Jpn J Cancer Res 80:981–987

    PubMed  Google Scholar 

  • Landy A, Gartland GL, Clement LT, (1983) Characterization of phenotypically distinct subpopulation of Leu2+ cells that suppresses T-cell proliferative responses. J Immunol 131:1757–1762

    Google Scholar 

  • Loeffler CM, Smyth MJ, Longo DL, Kopp WC, Harvery LK, Tribble HR, Tase JE, Urba WJ, Leonard AS, Young HA, Ochoa AC (1992) Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8− T cells. J Immunol 149:949–956

    PubMed  Google Scholar 

  • Mukherji B, Wilhelm SA, Guha A, Ergin MT (1986) Regulation of cellular immune response against autologous human melanoma. I. Evidence for cell-mediated suppression of in vitro cytotoxic immune response. J Immunol 136:1888–1892

    PubMed  Google Scholar 

  • Rosenberg SA, Lotze MT, Muul SE, Leitman AE, Chang SE, Ettinghausen YL, Matory JM, Skibber E, Shiloni JT, Vetto CA, Seipp C, Simpson C, Reichert CM (1985) Observation on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492

    PubMed  Google Scholar 

  • Takahashi K, Ono K, Hirabayashi Y, Taniguchi M (1988) Escape mechanisms of melanoma from immune system by soluble melanoma antigen. J Immunol 140:3244–3248

    PubMed  Google Scholar 

  • Takei F, Levy JG, Kilburn DG (1976) In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor-bearing mice. J Immunol 116:288–293

    PubMed  Google Scholar 

  • Takeuchi T, DiMaggio M, Levine H, Schlossman SF Morimoto C (1988) CD11 molecule defines two types of suppressor cells within the T8+ population Cell Immunol 111:398–409

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki 305, Japan

    Shohei Koyama

  2. Department of Surgery Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki 305, Japan

    Katashi Fukao

Authors
  1. Shohei Koyama
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  2. Katashi Fukao
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Koyama, S., Fukao, K. Phenotypic analysis of nylon-wool-adherent suppressor cells that inhibit the effector process of tumor cell lysis by lymphokine-activated killer cells in patients with advanced gastric carcinoma. J Cancer Res Clin Oncol 120, 240–247 (1994). https://doi.org/10.1007/BF01372563

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  • DOI: https://doi.org/10.1007/BF01372563

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