Summary
A controlled investigation of lymphocyte-mediated cytotoxicity has been carried out in patients with transitional cell carcinoma (TCC) of the urinary bladder, three long-term established cell lines with comparable sensitivities to the natural cytotoxicity (NC) being used as targets, namely HU 456 derived from human TCC, HU 609 from normal human urothelium, and SAOS 2 from a human osteosarcoma. The 44-h incubation microcytotoxicity assay (MA) was used with ‘blinded’ semiautomatic visual counting of target cells. The cytotoxicity was determined by titration with a serial dilution of lymphocyte suspensions 1:2, five different concentrations being used in each experiment. Fifty tests were performed with lymphocytes from 48 TCC patients. As controls, 65 patients with diseases other than TCC were tested simultaneously. The average cytotoxicity of lymphocytes from TCC patients against HU 456 was only slightly and insignificantly higher than that of the control patients. However, a marked decrease of the NC against the control cells HU 609 and SAOS 2 was noted with TCC patient lymphocytes.
After correction of the data for the depression of background NC, increased tumor-specific cytotoxicity (TSC) and tumor type-specific cytotoxicity (TTSC) were demonstrated in TCC patients with noninvasive malignant tumors (grade 2 or 3), whereas no increased specific cytotoxicity was found in TCC patients with invasive grade 2 or 3 tumors. Neither was any increased specific cytotoxicity found in patients with very well-differentiated grade tumors. The presence of specific reactivity in patients with noninvasive TCC in contrast to invasive TCC is supposed to indicate growth-controlling function of the cellular immune reaction.
Tests were also performed with lymphocytes from 35 patients in the postoperative phase without any history of TCC. Surprisingly, this group revealed a significantly elevated TSC but not increased TTSC when compared with the 65 untreated control patients, thus indicating that serious reservations must be made in the interpretation of the cytotoxocity assay.
Similar content being viewed by others
References
Akira D, Takasugi M (1977) Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum. Int J Cancer 19:747
Bean MA, 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
Bergkvist A, Ljungqvist A, Moberger G (1965) Classification of bladder tumors based on the cellular pattern. Acta Chir Scand 130:371
Bloom ET, Seeger RC (1976) Disease and non-disease-related cell-mediated cytotoxicity in humans. Cancer Res 36:1361
Bloom ET, Ossorio RC, Brosman SA (1974) Cell-mediated cytotoxicity against human bladder cancer. Int J Cancer 14:326
Brown JP, Belle G van, Hellström I (1976) Design of experiments using the microcytotoxicity assay. Int J Cancer 18:230
Bubenik J, Perlmann P, Helmstein K, Moberger G (1970) Immune response to urinary bladder tumors in man. Int J Cancer 5:39
Catalona WJ, Oldham RK, Herberman RB, Djeu JY, Cannon GB (1977) Lack of specificity of lymphocyte-mediated cytotoxicity against the bladder cancer cell line, T 24. J Urol 118:254
De Vries JE, Rümke P (1976) Tumor-associated lymphocyte cytotoxicity superimposed on ‘spontaneous’ cytotoxicity in melanoma patients. Int J Cancer 17:182
Dickmeiss E, Soeberg B, Svejgaard A (1977) Human cell-mediated cytotoxicity against modified target cells is restricted by HLA. Nature 270:526
Doherty PC, Götze D, Trinchieri G, Zinkernagel RM (1976) Models for recognition of virally modified cells by immune thymus-derived lymphocytes. Immunogenetics 3:517
Fujimoto S, Matsuzawa T, Nakagawa K, Tada T (1978) Cellular interaction between cytotoxic and suppressor T cells against syngeneic tumors in the mouse. Cell Immunol 38:378
Goulmy E, Termijtelen A, Bradley BA, van Rood JJ (1977) Yantigen killing by T cells of women is restricted by HLA. Nature 266:544
Hakala TR, Lange PH, Castro A, Elliott A, Fraley EE (1974) Cell-mediated cytotoxicity against human transitional cell carcinomas of the genitourinary tract. Cancer 34:1929
Hellström I, Hellström KE, Sjörgen HO, Warner GA (1971) Demonstration of cell-mediated immunity to human neoplasms of various histological types. Int J Cancer 7:1
Jerrells TR, Dean JH, Richardson GL, McCoy JL, Herberman RB (1978) Role of suppressor cells in depression of in vitro lymphoproliferative responses of lung cancer and breast cancer patients. J Natl Cancer Inst 61:1001
Kristensen E, Langvad E (1978) Natural cytotoxicity. Cancer Immunol Immunother 5:71
Kristensen E, Reimann R (1977) Direct cytotoxicity test applied to patients in stage I and II of malignant skin melanoma. Cancer Immunol Immunother 2:49
Levy NL (1978) Specificity of lymphocyte-mediated cytotoxicity in patients with primary intracranial tumors. J Immunol 121:903
Moore M, Robinson N (1977) Cell-mediated cytotoxicity in carcinoma of the human urinary bladder. Cancer Immunol Immunother 2:233
O'Toole C, Perlmann P, Unsgaard B, Moberger G, Edsmyr F (1972a) Cellular immunity to human urinary bladder carcinoma. I. Correlation to clinical stage and radiotherapy. Int J Cancer 10:77
O'Toole C, Perlmann P, Unsgaard B, Almg»rd LE, Johansson B, Moberger G, Edsmyr F (1972b) Cellular immunity to human urinary bladder carcinoma. II. Effect of surgery and preoperative irradiation. Int J Cancer 10:92
Pross HF, Baines MG (1976) Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. I. The effect of malignant disease. Int J Cancer 18:593
Takasugi M, Mickey MR, Terasaki PI (1973) Reactivity of lymphocytes from normal persons on cultured tumor cells. Cancer Res 33:2898
Takasugi M, Koide Y, Akira D, Ramseyer A (1977) Specificities in natural cell-mediated cytotoxicity by the cross-competition assay. Int J Cancer 19:291
Trinchieri G, Aden DP, Knowles BB (1976) Cell-mediated cytotoxicity to SV 40-specific tumor-associated antigens. Nature 261:312
Troye M, Perlmann P, Larsson Å, Blomgren H, Johansson B (1977) Cellular cytotoxicity in vitro in transitional cell carcinoma of the human urinary bladder: 51Cr-release assay. Int J Cancer 20:188
Troye M, Vilien M, Pape GR, Perlmann P (1980) Cytotoxicity in vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or antologous tumor cells derived from established cell lines or short-term cultures. Int J Cancer 25:33
Vanky F, Klein E, Stjernsward J, Rodrigues L, Peterffy A, Steiner L, Nilsonne U (1978) Human tumor-lymphocyte interaction in vitro. III. T lymphocytes in autologous tumor stimulation (ATS). Int J Cancer 22:679
Vilien M, Wolf H (1978) The specificity of the microcytotoxicity assay for cell-mediated immunity in human bladder cancer. J Urol 119:338
Yu A, Watts H, Jaffe N, Parkman R (1977) Concomitant presence of tumor-specific cytotoxic and inhibitor lymphocytes in patients with osteogenic sarcoma. N Engl J Med 297:121
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vilien, M., Wolf, H. & Rasmussen, F. Titration of natural and disease-related cytotoxicity of lymphocytes from bladder cancer patients. Cancer Immunol Immunother 8, 189–195 (1980). https://doi.org/10.1007/BF00205671
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205671