Skip to main content
SpringerLink
Log in

Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer: Decreased LAK cytotoxicity caused by a low incidence of CD56+ and CD57+ mononuclear blood cells

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in51Cr-release assays. The PBMC subsets were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P<0.05). The percentages of PBMC positive for the NK-cell markers CD56 and CD57 were lowest in the patients and were correlated to the decrease in cytotoxicity. Depletion of CD56+ or CD57+ cells from PBMC prior to or after 2 days stimulation with IL-2 demonstrated that these cells are the major source of LAK-cell cytotoxicity and showed that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA: The lymphokine activated killer cell phenomenon: Lysis of NK resistant fresh solid tumor cells by IL-2 activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841, 1982

    Google Scholar 

  2. Hogan PG, Basten A: What are killer cells and what do they do. Immunohaematol 2:50–58, 1988

    Google Scholar 

  3. Phillips JH, Lanier LL: Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 164:814–825, 1988

    Google Scholar 

  4. Lanier LL, Le AN, Civin CI, Loken MR, Phillips JH: The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136:4480–4486, 1986

    Google Scholar 

  5. Lanier LL, Le AM, Phillips JH, Warner NL, Babcock GF: Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol 131:1789–1796, 1983

    Google Scholar 

  6. Catalona WJ, Tarpley JL, Potvin C, Chretien PB: Host immunocompetence in genitourinary cancer: Relation to tumour stage and prognosis. Natl Cancer Inst Monogr 49:105–110, 1978

    Google Scholar 

  7. Mukamel E, Shohat B, Servadio C: Immunological profile of patients with transitional cell carcinoma of the bladder. Br J Urol 54:11–15, 1982

    Google Scholar 

  8. O'Toole C, Perlmann P, Unsgaard B, Moberger G, Edsmyr F: Cellular immunity to human urinary bladder carcinoma. I. Correlation to clinical stage and radiotherapy. Int J Cancer 10:77–91, 1972

    Google Scholar 

  9. Perlmann P, O'Toole C, Unsgaard B: Lymphocyte-mediated tumor cell destructionin vitro. Some general principles and reactivities in human urinary bladder carcinoma. Natl Cancer Inst Monogr 35:223–229, 1972

    Google Scholar 

  10. Mestofi FK, Sobin LH, Torloni H: Histological typing of urinary bladder tumours. International Histological Classification of Tumours No. 10; Geneva, WHO; 1973

    Google Scholar 

  11. Böyum A: Isolation of leukocytes from human blood. Scand J Clin Lab Invest 21 (Suppl 97):77–89, 1968

    Google Scholar 

  12. Bubenik J, Baresova M, Viklicky V, Jakoubkova J, Sainerova H, Donner J: Established cell line of urinary bladder carcinoma (T24) containing tumour-specific antigen. Int J Cancer 11:765–773, 1973

    Google Scholar 

  13. Christensen B, Kieler J, Vilien M, Don P, Wang CY, Wolf H: A classification of human urothelial cells propagated in vitro. Anticancer Res 4:319–338, 1984

    Google Scholar 

  14. Vilien M, Christensen B, Wolf H, Rasmussen F, Hou-Jensen C, Povlsen CO: Comparative studies of normal, “spontaneously” transformed and malignant human urothelium cellsin vitro. Eur J Cancer Clin Oncol 19:775–789, 1983

    Google Scholar 

  15. Vilien M, Wolf H, Rasmussen F: Immunological characterization of cell lines established from malignant and normal human urothelium. Eur J Cancer 17:321–327, 1981

    Google Scholar 

  16. Bolhuis RLH, van der Griend R, Stoter G, Mukherji RJ: Lymphoid effector cells against tumor cells. Res Monogr Immunol 11:61–88, 1987

    Google Scholar 

  17. Chapple MR, Johnson GD, Davidson RS: Fluorescence quenching of fluorescein by R-phycoerythrin. A pitfall in dual fluorescence analysis. J Immunol Meth 111:209–214, 1988

    Google Scholar 

  18. Miltenyi S, Müller W, Weichel W, Radbruch A: High gradient magnetic cell separation with MACS. Cytometry 11:231–238, 1990

    Google Scholar 

  19. Siegel S, Castellan NJ: Nonparametric Statistics for the Behavioral Sciences. New York, McGraw-Hill, 1988

    Google Scholar 

  20. Bubenik J, Kieler J, Tromholt V, Hermann G, Jandlová, T: Defect in lectin-induced interleukin 2 production by peripheral blood lymphocytes of patients with invasive urinary bladder carcinoma. Immunol Lett 18:115–118, 1988

    Google Scholar 

  21. Bosnes V, Hirschberg H: Comparison ofin vitro glioma cell cytotoxicity of LAK cells from patients and healthy subjects. J Neurosurg 69:234–238, 1988

    Google Scholar 

  22. Grimm EA, Robb RJ, Roth JA, Neckers LM, Lackman LB, Wilson DJ, Rosenberg SA: Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells. J Exp Med 158:1356–1361, 1983

    Google Scholar 

  23. Lanier LL, Phillips JH: What are natural killer cells? ISI Atlas of Science, Immunology 1988, pp 15–18

  24. Sawada H, Abo T, Sugawara S, Kumagai K: Prerequisite for the induction of lymphokine-activated killer cells from T lymphocytes. J Immunol 140:3668–3673, 1988

    Google Scholar 

  25. Ellis TM, Fisher RI: Functional heterogeneity of Leu19bright+ and Leu19dim+ lymphokine-activated killer cells. J Immunol 142:2949–2954, 1989

    Google Scholar 

  26. Ellis TM, Creekmore SP, McMannis JD, Braun DP, Harris JA, Fisher RI: Appearance and phenotypic characterization of circulating Leu19+ cells in cancer patients receiving recombinant interleukin 2. Cancer Res 48:6597–6602, 1988

    Google Scholar 

  27. McMannis JD, Fisher RI, Crekmore SP, Braun DP, Harris JE, Ellis JE:In vivo effects of recombinant IL-2. I. Isolation of circulation Leu-19+ lymphokine-activated killer effector cells from cancer patients receiving recombinant IL-2. J Immunol 140:1335–1340, 1988

    Google Scholar 

  28. Schmidt RE, Hercend T, Fox DA, Bensussan A, Bartley G, Daley JF, Schlossman SF, Reinhertz EF, Ritz J: The role of interleukin 2 and T11 E rosette antigen in activation and proliferation of human NK clones. J Immunol 135:672–678, 1985

    Google Scholar 

  29. Tilden AB, Itoh K, Balch CM: Human lymphokine-activated killer (LAK) cells: Identification of two types of effector cells. J Immunol 138:1068–1073, 1987

    Google Scholar 

  30. Van de Griend RJ, Tax WJM, van Krimpen BA, Vreugdenhil RJ, Ronteltap CP, Bolhuis RL: Lysis of tumor cells by CD3+4−8−16+ T cell receptor alpha beta− clones, regulated via CD3 and CD16 activation sites, recombinant interleukin 2, and interferon beta. J Immunol 138:1627–1633, 1987

    Google Scholar 

  31. Herberman RB, Hiserodt J, Vujanovic N, Balch C, Lotzova E, Bolhuis R, Golub S, Lanier LL, Phillips JH, Riccardi C, Ritz J, Santoni A, Schmidt RE, Uchida A: Lymphokine-activated killer cell activity. Characteristics of effector cells and their progenitors in blood and spleen. Immunol Today 8:178–181, 1987

    Google Scholar 

  32. Phillips JH, Lanier LL: Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol 136:1579–1585, 1986

    Google Scholar 

  33. Ulmer AJ, Scholz W, Ernst M, Flad HD: Response of human T lymphocytes to phytohemagglutinin (PHA) after sequential depletion of monocytes, HLA-DR+, Leulla+, and Leu7+ cells. Immunobiology 170:419–433, 1985

    Google Scholar 

  34. Perussia B, Fanning V, Trinchieri G: A human NK and K cell subset shares with cytotoxic T cells expression of the antigen recognized by antibody OKT8. J Immunol 131:223–231, 1983

    Google Scholar 

  35. Hudson L, Hay FC: Lymphocytes and effector cells.In Practical Immunology, L Hudson, FC Hay (eds). Oxford, London, Blackwell Scientific, 1989, pp 171–172

    Google Scholar 

  36. Aribia MB, Moiré N, Métivier D, Vaquero C, Lantz O, Olive D, Charpentier B, Senik A: Il-2 receptors on circulating natural killer cells and T lymphocytes. J Immunol 142:490–495, 1989

    Google Scholar 

  37. Smith KA: Interleukin 2; Inception, impact, and implications. Science 240:1169–1176, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Ndr. Frihavnsgade 70, DK-2100, Copenhagen, Denmark

    Gregers G. Hermann & Jesper Zeuthen

  2. Department of Urology, Herlev University Hospital, DK-2730, Herlev, Denmark

    Kresten R. Petersen & Kenneth Steven

Authors
  1. Gregers G. Hermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kresten R. Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth Steven
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jesper Zeuthen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hermann, G.G., Petersen, K.R., Steven, K. et al. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer: Decreased LAK cytotoxicity caused by a low incidence of CD56+ and CD57+ mononuclear blood cells. J Clin Immunol 10, 311–320 (1990). https://doi.org/10.1007/BF00917476

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00917476

Key words

Search

Navigation