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Disease-related lymphocyte cytotoxicity in vitro in patients with transitional cell carcinoma of the urinary bladder. Comparisons with other malignancies, acute cystitis, and healthy donors

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Summary

Blood lymphocytes from 100 patients with transitional cell carcinoma of the urinary bladder (TCC-bladder) were studied for their cytotoxicity in vitro against a panel of allogeneic tissue culture cell lines. Of the TCC-bladder patients, 45 were untreated for their disease, while 55 had been treated with local radiotherapy up to 12 years before testing. Control lymphocytes were obtained from (1) 45 untreated, age- and sex-matched patients with other neoplastic diseases, mainly urogenital cancers; (2) 19 patients with acute cystitis; and (3) 45 healthy donors. Lymphocytes from individual donors within all five groups were frequently cytotoxic to any one of the target cells. However, the lymphocytes from each of the two TCC-bladder groups were markedly more cytotoxic to two different bladder tumor targets than to control targets derived from normal bladder epithelium, from colon carcinoma, or from malignant melanoma. Similar comparisons made within each of the three control donor groups did not show this. The results indicate that the two bladder tumor targets were not more susceptible to lymphocyte-mediated lysis than the control targets. The mean cytotoxicity displayed by the lymphocytes from both TCC-bladder groups to the bladder tumor targets was significantly higher than that of the cancer control group and that of the healthy donors. No such elevation was seen when the cancer control group or the cystitis patients were compared with healthy donors. Although untreated TCC-patients with a larger tumor burden (stages T3–T4) appeared to be slightly less cytotoxic to all target cells than those with a smaller tumor burden (T1–T2), these differences were not statistically significant. On the other hand, among the treated TCC-patients, in the main those tested more than 1 year and up to 5 years after therapy exhibited a significantly elevated mean cytotoxicity to the bladder tumor targets. Within all five donor groups, the overall cytotoxicity to the bladder tumor targets and the normal bladder targets showed a statistically highly significant correlation. However, while there was no correlation for the untreated TCC-bladder patients and the clinical controls between cytotoxicity to the bladder tumor targets on one hand and non-bladder targets on the other, the cytotoxicity to the bladder tumor targets of the treated TCC-bladder patients was also correlated with that to the colon carcinoma and the melanoma targets. The results indicate that cytotoxicity in both TCC patients and controls reflects recognition by the lymphocytes of a variety of antigens, shared to different degrees by different groups of target cells. Furthermore, in TCC-bladder patients there is a superimposed cytotoxicity, which is related to their disease and which probably reflects reactions against one or several tumor-associated antigens.

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References

  1. Akira D, Takasugi M (1977) Loss of specific natural mediated cytotoxicity with absorption of natural antibodies from serum. Int J Cancer 19:747–755.

    Google Scholar 

  2. Armitage P (1971) Statistical methods in medical research. Blackwell, London.

    Google Scholar 

  3. Baldwin RW (1975) In vitro assays of cell-mediated immunity to human solid tumors: problems of quantitation, specificity and interpretation. J. Natl Cancer Inst 55:745–748.

    Google Scholar 

  4. Baldwin RW, Embleton MJ (1977) Assessment of cell-mediated immunity to human tumour associated antigens. Int Rev Exp Pathol 17:49–56.

    Google Scholar 

  5. Bean MW, Pees H, Fogh JE, Grabstald H, Oettgen HF (1974) Cytotoxicity of lymphocytes from patients with cancer of the urinary bladder: detection by a 3H-proline microcytotoxicity test. Int J Cancer 14:186–195.

    Google Scholar 

  6. Bean M, Bloom B, Herberman R, Old L, Oettgen H, Klein G, Terry W (1975) Cell-mediated cytotoxicity for bladder carcinoma. Evaluation of a workshop. Cancer Res 35:2902–2913.

    Google Scholar 

  7. Bloom ET, Seeger RC (1976) Disease and non-disease-related cell-mediated cytotoxicity in humans. Cancer Res 36:1361–1366.

    Google Scholar 

  8. Bloom ET, Ossario RC, Brosman SA (1974) Cell-mediated cytotoxicity against human bladder cancer. Int J Cancer 14:326–334.

    Google Scholar 

  9. Bolhuis RLH (1977) Cellular microcytotoxicity in a human bladder cancer system: Analysis of in vitro lymphocyte-mediated cytotoxicity against cultured target cells. Cancer Immunol Immunother 2:245–256.

    Google Scholar 

  10. Bonnard GD, West WH (1979) Cell-mediated cytotoxicity in humans. A critical review of experimental models and clinically oriented studies. In: Herberman RB and McIntire VR (eds) Immunodiagnosis of cancer. Marcel Dekker, New York (In press).

    Google Scholar 

  11. Bubenik J, Perlmann P, Helmstein K, Moberger G (1970a) Cellular and humoral immune responses to human urinary bladder carcinoma. Int J Cancer 5:316–319.

    Google Scholar 

  12. Bubenik J, Perlmann P, Helmstein K, Moberger G (1970b) Immune response to human urinary bladder tumors in man. Int J Cancer 5:39–46.

    Google Scholar 

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

    Google Scholar 

  14. Cannon GB, Bonnard GD, Djeu J, West WH, Herberman RB (1977) Relationship of human natural lymphocyte-mediated cytotoxicity to cytotoxicity of breast cancer-derived target cells. Int J Cancer 19:487–497.

    Google Scholar 

  15. Catalona JW, Oldham RK, Herberman RB, Djeu JY, Cannon GB (1977) Lack of specificity of lymphocyte-mediated cytotoxicity against the bladder cancer cell line, T24. J Urol 118:254–257.

    Google Scholar 

  16. Documenta Geigy Scientific Tables, 6th ed. (1964) Geigy Basle.

  17. Fogh J (ed) (1975) Human tumor cells in vitro. Plenum Press, New York.

    Google Scholar 

  18. Hammarström S, Troye M, Wahlund G, Svenberg T, Perlmann P (1977) K-cell mediated lysis of cultured colon carcinoma and urinary bladder carcinoma cells induced by mono-specific antisera against carcinoembryonic antigen (CEA) and two CEA-related normal glycoproteins. Int J Cancer 19:756–766.

    Google Scholar 

  19. Heppner GH, Stalbach L, Byrne M, Cummings FJ, McDonough E, Calabresi P (1973) Cell-mediated reactivity to tumor antigens in patients with malignant melanoma. Int J Cancer 11:245–260.

    Google Scholar 

  20. Herberman RB, Holden HT (1978) Natural cell-mediated immunity. Adv Cancer Res 27:305–377.

    Google Scholar 

  21. Herberman RB, Oldham RK (1975) Problems associated with study of cell-mediated immunity to human tumors by microcytotoxicity assays. J Natl Cancer Inst 55:749–753.

    Google Scholar 

  22. Kiessling R, Haller O (1978) Natural killer cells. In: Warner N, Cooper M (eds) Contemporary topics in immunobiology, vol. 8. Plenum Press, New York, p 171.

    Google Scholar 

  23. Kiuchi M, Takasugi M (1976) The non-selective cytotoxic cell (N-cell). J Natl Cancer Inst 56:575–582.

    Google Scholar 

  24. Koide Y, Takasugi M (1977) Determination of specificity in natural cell-mediated cytotoxicity by natural antibodies. J Natl Cancer Inst 59:1099–1105.

    Google Scholar 

  25. Moore M, Robinson N (1977) Cell-mediated cytotoxicity in carcinoma of the human urinary bladder. Cancer Immunol Immunother 2:233–243.

    Google Scholar 

  26. Mukherji B, Vassas D, Flowers S, Binder SC, Nathonsson L (1975) Selective and non-selective lymphocytotoxicity in human melanoma: observation on the effect of long-term culture and fetal bovine serum on target-cell sensitivity to lymphocytes. Int J Cancer 16:971–980.

    Google Scholar 

  27. Oldham RK, Siwarski D, McCoy JL, Plata EJ, Herberman RB (1973) Evaluation of a cell-mediated cytotoxicity assay utilizing 125Iododeoxyuridine-labeled tissue culture target cells. Natl Cancer Inst Monogr 37:49–58.

    Google Scholar 

  28. O'Toole C, Perlmann P, Unsgaard B, Almg»rd LE, Johansson B, Moberger G, Edsmyr F (1972a) Cellular immunity to human urinary bladder carcinoma. II. Effect of surgery and preoperative irradiation. Int J Cancer 10:92–98.

    Google Scholar 

  29. O'Toole C, Perlmann P, Unsgaard B, Almg»rd LE, Johansson B, Moberger G, Edsmyr F (1972b) Cellular immunity to human urinary bladder carcinoma. I. Correlation to clinical stage and radiotherapy. Int J Cancer 10:77–91.

    Google Scholar 

  30. O'Toole C, Unsgaard B, Almg»rd LE, Johansson B (1973) The cellular immune response to clinical stage and treatment. Br J Cancer (Suppl) 28:266–275.

    Google Scholar 

  31. O'Toole C, Helmstein K, Perlmann P, Moberger G (1975) Cellular immunity to transitional cell carcinoma of the urinary bladder. III. Effects of hydrostatic pressure. Int J Cancer 16:413–426.

    Google Scholar 

  32. Pape GR, Troye M, Perlmann P (1977) Characterization of cytolytic effector cells in peripheral blood of healthy individuals and cancer patients. II. Cytotoxicity to allogeneic or autochtonous tumor cells in tissue culture. J Immunol 118:1925–1930.

    Google Scholar 

  33. Pape GR, Troye M, Axelsson B, Perlmann P (1979) Simultaneous occurrence of immunoglobulin and immunoglobulin independent mechanisms in natural cytotoxicity of human lymphocytes. J Immunol (In press).

  34. Perlmann P, Cerottini JC (1979) In: Sela M (ed) The antigens, vol. 5. Academic Press, New York, p 173.

    Google Scholar 

  35. Perlmann H, Perlmann P, Pape GR, Halldén G (1976) Purification, fractionation and assay of antibody-dependent lymphocytic effector cells (K cells) in human blood. Scand J Immunol [Suppl 5] 5:57–68.

    Google Scholar 

  36. Peter HH, Eife RF, Kalden JR (1976) Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator. J Immunol 116:342–348.

    Google Scholar 

  37. Rosenberg EB, McCoy JL, Green SS, Donelly FC, Siwarski DF, Levine PH, Herberman RB (1974) Destruction of human lymphoid tissue culture cell lines by human peripheral lymphocytes in 51Cr-release cellular cytotoxicity assays. J Natl Cancer Inst 52:346–352.

    Google Scholar 

  38. Snedecor GW (1956) Statistical methods. Iowa State University Press, Ames.

    Google Scholar 

  39. Takasugi M, Mickey MR (1976) Interaction analysis of selective and non-selective cell-mediated cytotoxicity. J Natl Cancer Inst 57:255–261.

    Google Scholar 

  40. Takasugi M, Mickey MR, Terasaki PI (1973) Reactivity of lymphocytes from normal persons on cultured tumor cells. Cancer Res 33:2898–2902.

    CAS  PubMed  Google Scholar 

  41. Takasugi M, Akira D, Takasugi J, Mickey MR (1977) Specificities in human cell-mediated cytotoxicity. J Natl Cancer Inst 59:69–75.

    Google Scholar 

  42. Troye M, Perlmann P, Larsson Å, Blomgren H, Johansson B (1977a) Cellular cytotoxicity in vitro in transitional cell carcinoma of the human urinary bladder: 51Cr-release assay. Int J Cancer 20:188–198.

    Google Scholar 

  43. Troye M, Perlmann P, Pape GR, Spiegelberg HL, Näslund I, Gidlöf A (1977b) The use of Fab-fragments of rabbit anti-human immunoglobulins as analytic tools for establishing the involvement of immunoglobulins in the spontaneous cytotoxicity of lymphocytes from patients with bladder carcinoma and from healthy donors. J Immunol 119:1061–1067.

    Google Scholar 

  44. Troye M, Hansson Y, Paulie S, Perlmann P, Blomgren H, Johansson B (1980a) Lymphocyte mediated lysis of tumor cells in vitro (ADCC) induced by serum antibodies from patients with urinary bladder carcinoma or controls. Int J Cancer 25:45–51.

    Google Scholar 

  45. Union Internationale Contre le Cancer (1974) TNM Classification of malignant tumors. UICC, Geneva.

    Google Scholar 

  46. Unsgaard B, O'Toole C (1975) Influence of tumor burden and therapy on cellular cytotoxicity responses in patients with ocular and skin melanoma. Br J Cancer 31:301–316.

    Google Scholar 

  47. Vilien M, Wolf H (1978) The specificity of the microcytotoxicity assay for cell-mediated immunity in human bladder cancer. J Urol 119:338–342.

    Google Scholar 

  48. Vose BM, Vanky F, Fopp M, Klein E (1978) In vitro generation of cytotoxicity against autologous human biopsy cells. Int J Cancer 21:588–593.

    Google Scholar 

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Authors and Affiliations

  1. Department of Immunology, University of Stockholm, S-106 91, Stockholm, Sweden

    M. Troye, Å. Larsson, S. Paulie, M. Karlsson & P. Perlmann

  2. Medical Clinic II, University of Munich, Großhadern, 8000, Munich, Germany

    G. R. Pape

  3. Radiumhemmet, Karolinska Hospital, WHO Collaborating Center for Research and Treatment of Urinary Bladder Cancer, S-104 01, Stockholm, Sweden

    H. Blomgren

  4. Department of Urology, Karolinska Hospital, WHO Collaborating Center for Research and Treatment of Urinary Bladder Cancer, S-104 01, Stockholm, Sweden

    B. Johansson

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  1. M. Troye
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  4. S. Paulie
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Troye, M., Pape, G.R., Larsson, Å. et al. Disease-related lymphocyte cytotoxicity in vitro in patients with transitional cell carcinoma of the urinary bladder. Comparisons with other malignancies, acute cystitis, and healthy donors. Cancer Immunol Immunother 8, 13–26 (1980). https://doi.org/10.1007/BF00206349

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  • DOI: https://doi.org/10.1007/BF00206349

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