Summary
Human tumor and normal cell lines in culture were examined for the release of factors capable of inhibiting lymphocyte blastogenesis. Supernatants from tumor cell cultures of melanoma, carcinoma (lung, colon, breast), sarcoma, and normal fibroblasts inhibited normal lymphocyte response to PHA. Only supernatants from the tumor cell lines C1 (colon carcinoma), 734B (breast carcinoma), and 231 (breast carcinoma) were found to inhibit both PHA and ConA responses significantly. The two breast carcinoma cell lines, 734B and 231, which also were capable of inhibiting lymphocyte responses to PPD and alloantigens, were investigated further. The inhibition of lymphocyte blastogenesis caused by the supernatant of these two cell lines could not be overcome by the addition of added mitogen. Further experiments showed that the inhibition was not due to nutrient deficiencies and the supernatants were not directly toxic to the lymphocyte cultures as judged by trypan blue exclusion.
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Anderson RJ, McBride CM, Hersh EM (1972) Lymphocyte blastogenic responses to cultured allogeneic tumor cells in vitro. Cancer Res 32:988
Baldwin RW, Embleton MJ, Price MR, Robins A (1974) Immunity in the tumor bearing host and its modification by serum factor. Cancer 34:1452
Bonnard GD, Manders EK, Campbell DA, Herberman RB, Collins MJ (1976) Immunosuppressive activity of a subline of the mouse EL-4 lymphoma; evidence for minute virus of mice causing the inhibition. J Exp Med 143:187
Brandchaft PB, Aoki T, Silverman TN (1976) Immunologic and immunosuppressive components in soluble preparations from Moloney murine leukemia virus-induced tumor cells. Int J Cancer 17:678
Curtis LK, Edgington TS (1976) Regulatory serum lipoproteins: regulation of lymphocyte stimulation by a species of low density lipoprotein. J Immunol 116:1452
DeLustro F, Argyris BF (1976) Mechanism of mastocytoma-mediated suppression of lymphocyte reactivity. J Immunol 117:2073
Fisher B, Saffer EA, Fisher ER (1972) Studies concerning the regional lymph nodes in cancer. III. Response of regional lymph node cells from breast and colon cancer patients to PHA stimulation. Cancer 30:1202
Gisler RH, Fridman WH (1975) Suppression of in vitro antibody synthesis by immunoglobulin binding factor. J Exp Med 142:507
Glaser M, Kirchner H, Holden HT, Herberman RB (1976) Inhibition of cell mediated cytotoxicity against tumor associated antigens by suppressor cells from tumor bearing mice. J Natl Cancer Inst 56:865
Golub SH, Sulit HL, Morton DL (1975) The use of viable frozen lymphocytes for studies in human tumor immunology. Transplantation 19:195
Hanna N, Kalderon R, Nelken D (1975) Inhibition of T and B lymphocyte functions by normal immunosuppressive protein. Immunology 29:433
Hellstrom KE, Hellstrom I (1974) Lymphocyte-mediated cytotoxicity and blocking serum activity to tumor antigens. Adv Immunol 18:209
Hersh EM, Drewinko B (1974) Specific inhibition of lymphocyte blastogenic responses to mitogens by a factor produced by cultured human malignant lymphoma cells. Cancer Res 34:215
Hersh EM, McCredie KB, Freireich EJ (1974a) Inhibition of in vitro lymphocyte blastogenesis by inhibitor produced by cultured human lymphoblasts. Clin Exp Immunol 1:463
Hersh EM, McCredie KB, Freireich EJ (1974b) Mechanism of production of inhibitor of lymphocyte blastogenic response to mitogens by cultured lymphoblastoid cell line cells. Transplantation 17:221
Holmes EC, Golub SH (1976) Immunologic defects in lung cancer patients. J Thorac Cardiovasc Surg 71:161
Hrsak I, Marotti T (1973) Immunosuppression mediated by Ehrlich ascites fluid. Eur J Cancer 9:717
Kamo I, Patel C, Kateley J, Friedman H (1975) Immunosuppression induced in vitro by mastocytoma cells and cell-free extracts. J Immunol 114:1749
Katz DH, Benacerraf B (1972) The regulatory influence of activated T cells on B cell responses to antigen. Adv Immunol 15:1
Kirkwood JM, Gershon RK (1974) A role for suppressor T cells in immunological enhancement of tumor growth. Prog Exp Tumor Res 19:157
Mannick JA, Schmid K (1967) Prolongation of allograft survival by an alpha globulin isolated from normal blood. Transplantation 5:1231
Morton DL, Holmes EC, Eilber FR, Wood WC (1971) Immunological aspects of neoplasia: A rational basis for immunotherapy. Ann Intern Med 74:587
Nimberg RB, Glasgow AH, Menzoian JU, Constantian MB, Cooperband SR, Mannick JA, Schmid K (1975) Isolation of an immunosuppressive peptide fraction from the serum of cancer patients. Cancer Res 3:1489
Occhino JC, Glasgow AH, Cooperband SR, Mannick JA, Schmid K (1973) Isolation of an immunosuppressive peptide fraction from human plasma. J Immunol 110:685
Remacle-Bonnet MM, Pommier GJ, Kaplanski S, Range RJ, Depieds RC (1976) Inhibition of normal allogeneic lymphocyte mitogenesis by a soluble inhibition extracted from human colonic carcinoma. J Immunol 117:1145
Rich RR, Pierce CW (1974) Biological expression of lymphocyte activiation. III. Suppression of plaque-forming cell responses in vitro by supernatant fluids from ConA activated spleen cell cultures. J Immunol 112:1360
Sinkovics JG, Cabiness JR, Shullenberger CC (1972a) Monitoring in vitro immune reactions to solid tumors. Front Radiat Ther Oncol 7:99
Sinkovics JG, Reeves WJ, Cabiness JR (1972b) Cell-and antibody-mediated immune reactions of patients to cultured cells of breast carcinoma. J Natl Cancer Inst 48:1145
Takei F, Levy JG, Kilburn DG (1977) Characterization of suppressor cells in mice bearing syngeneic mastocytoma. J Immunol 118:412
Thomas DW, Roberts WK, Talmage DW (1975) Regulation of the immune response: production of a soluble suppressor by immune spleen cells in vitro. J Immunol 114:343
Thurman GB, Strong DM, Ahmed A, Green SS, Sell KW, Hartzman RJ, Bach FH (1973) Human mixed lymphocyte cultures. Evaluation of a microculture technique using the multiple automated sample harvester (mash). Clin Exp Immunol 15:289
Vogelfanger IJ, Milthorp P, Behelak Y, Barron PT, Steele D, Richter M (1975) Naturally occurring immunosuppressive agents. I. The presence in normal pig liver of a factor possessing immunosuppressive properties with respect to pig lymphoid cells in vitro. Transplantation 20:130
Vogelfanger IJ, Milthorp P, Behelak Y, Barron PT, Steele D, Richter M (1976) Naturally occurring immunosuppressive agents. II. The ability of cell-free liver extracts to modify the rejection of allogeneic skin graft in the rabbit. Immunol Commun 5:125
Voorting-Hawking M, Michael JG (1977) Isolation and characterization of immunoregulatory factor from normal human serum. I. Preliminary biochemical and biological characterization of immunosuppressive factor. J Immunol 118:505
Wanebo HJ, Hansen J, Rosen P, Thaler H, Robbins G, Urban J, Oettgen H (1976) Immunologic reactivity in patients with operable breast cancer. In: Cripsen RG (ed) Neoplasm immunity: Mechanisms. ITR, Chicago, pp 167–183
Whitney RB, Levy JG (1975) Effects of sera from tumor bearing mice on mitogen and allogeneic cell stimulation of normal lymphoid cells. J Natl Cancer Inst 54:733
Whittaker MG, Rees K, Clark CG (1971) Reduced lymphocyte transformation in breast cancer. Lancet 1:892
Zoller M, Price MR, Baldwin RW (1976) Inhibition of cell mediated cytotoxicity to chemically induced rat tumor by soluble tumor and embryo cell extracts. Int J Cancer 17:129
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Renk, C.M., Gupta, R.K. & Morton, D.L. Inhibition of normal allogeneic lymphocyte mitogenesis by a factor released from human tumor cells in culture. Cancer Immunol Immunother 11, 7–16 (1981). https://doi.org/10.1007/BF00205768
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DOI: https://doi.org/10.1007/BF00205768