Summary
Blood lymphocytes from cancer patients frequently showed reduced responsiveness to mitogens compared with those from healthy individuals. This impairment did not appear to be attributable to an intrinsic T cell deficit but to the involvement of suppressor cells. The role of monocytes as suppressors in cancer patients was supported by experiments in which they were depleted by removal of adherent cells or selectively eliminated in situ by treatment with macrophage toxic agents (carrageenan, silica). Phytomitogen responses were consistently elevated by these manoeuvres. Indomethacin elevated responses in unseparated but not adherent cell depleted populations, indicating an important role for prostaglandins in this phenomenon. None of these procedures markedly influenced the response of lymphocytes from healthy individuals.
Following removal of adherents, response could be generated or increased in SRBC rosetting or non-rosetting fractions depending upon the initial responsiveness of the adherent depleted populations, an observation consistent with the coexistence of responder and suppressor populations. Tumour-draining lymph node cells differed from peripheral blood insofar as no evidence of monocyte-like suppressors was found, but SRBC rosetting cells depressed the mitogen stimulation of autologous blood lymphocytes.
These data establish that suppressor cells are operative in the depression of T cell responses to mitogens and indicate that several cell types are involved.
Similar content being viewed by others
References
Argyris BF (1977) Suppressor cells in the spleen of tumor-allosensitised mice. Cancer Res 37:3390
Baird LG, Kaplan AM (1977) Macrophage regulation of mitogen-induced blastogenesis. I. Demonstration of the inhibitory cells in the spleens and peritoneal exudates of mice. Cell Immunol 28:22
Barrett O (1970) Monocytosis in malignant disease. Ann Intern Med 73:991
Bean MA, Kodera Y, Cummings KB, Bloom BR (1977) Occurrence of restricted suppressor T-cell activity in man. J Exp Med 146:1455
Birnbaum G, Swick L (1978) Human suppressor lymphocytes. I. Induction and characterisation. Cell Immunol 40:16
Broder S, Muul MS, Waldemann TA (1978) Suppressor cells in neoplastic disease. J Natl Cancer Inst 61:5
Catalona WJ, Ratliff TL, McCool RE (1979) Concanavalin A-inducible suppressor cells in regional lymph nodes of cancer patients. Cancer Res 39:4372
Dent PB, Louis JA, McCulloch PB, Dunnett CW, Cerottini JC (1980) Correlation of elevated Clq binding activity and CEA levels with clinical features and prognosis in bronchogenic carcinoma. Cancer 45:130
Eilber FR, Morton DL (1970) Improved immunologic reactivity and recurrence following cancer surgery. Cancer 25:362
Engleman EG, McDevitt HO (1978) A suppressor T cell of the mixed lymphocyte reaction specific for the HLA-D region in man. J Clin Invest 61:828
Fujimoto S, Greene MI, Sehon AH (1976) Regulation of the immune response to tumor antigens. II. The nature of the immunosuppressor cells in tumor-bearing hosts. J Immunol 116:800
Goodwin JS, Messner RP (1979) Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70. J Clin Invest 64:434
Goodwin JS, Bankhurst AD, Messner RP (1977) Suppression of human T-cell mitogenesis by prostaglandin. Existence of prostaglandin-producing suppressor cell. J Exp Med 146:1719
Goodwin JS, Messner RP, Bankhurtst AD, Peake GT, Saiki JH, Williams RC (1977) Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med 297:963
Han T, Takita H (1979) Depression of T lymphocyte response by non-T suppressor cells in lung cancer patients. Cancer 44:2090
Hedfors E, Holm G, Pettersson D (1975) Activation of human peripheral blood lymphocytes by Concanavalin A, dependence of monocytes. Clin Exp Immunol 22:223
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
Kirchner H, Muchmore AV, Chused TM, Holden HT, Herberman RB (1975) Inhibition of proliferation of lymphoma cells and T lymphocytes by suppressor cells from spleens of tumor-bearing mice. J Immunol 114:206
Kurland JI, Bockman R (1978) Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med 147:952
Lohrmann HP, Novikovs L, Graw RG Jr (1977) Cellular interaction in the proliferative response of human T and B lymphocytes to phytomitogens and allogeneic lymphocytes. J Exp Med 139:1553
Novogrodsky AK, Stenzel H, Rubin AL (1977) Stimulation of human peripheral blood lymphocytes by periodate, galactose oxidase soybean agglutinin and peanut agglutinin: Differential effects of adherent cells. J Immunol 118:852
Nyholm RE, Currie GA (1978) Monocytes and macrophages in malignant melanoma. II. Lysis of antibody-coated human erytrhocytes as an assay of monocyte function. Br J Cancer 39:3
Potter MR, Moore M (1975) PHA stimulation of separated human lymphocyte populations. Clin Exp Immunol 21:456
Potter MR, Moore M (1977) The effect of adherent and phagocytic cells on human lymphocyte PHA responsiveness. Clin Exp Immunol 27:159
Quan PC, Burtin P (1978) Demonstration of non-specific suppressor cells in the peripheral lymphocytes of cancer patients. Cancer Res 38:288
Rhodes J (1977) Altered expression of human monocyte Fc receptors in malignant disease. Nature 265:253
Rosenstreich DL, Farrar JJ, Dougherty S (1976) Absolute macrophage dependency of T lymphocyte activation by mitogens. J Immunol 116:131
Shou LS, Schwartz A, Good RA (1976) Suppressor cell activity after concanavalin A treatment of lymphocytes from normal donors. J Exp Med 143:1100
Simon L, Jones TL (1979) Re-evaluation of carrageenan cytotoxicity for macrophages. J Reticuloendothel Soc 25:133
Vose BM (1979) Functional activity of human tumor-infiltrating macrophages. Adv Exp Med Biol 114:783
Vose BM (to be published) Specific T-cell mediated killing of autologous lung tumour cells. Cell Immunol
Vose BM, Moore M (1979) Suppressor cell activity of lymphocytes infiltrating human lung and breast tumours. Int J Cancer 24:579
Vries JE de, Caviles AP Jr, Bont WS, Mendelsohn J (1979) The role of monocytes in human lymphocyte activation by mitogens. J Immunol 122:1099
Whittaker MG, Rees K, Clark CG (1971) Reduced lymphocyte transformation in breast cancer. Lancet I:892
Wing EJ, Remington JS (1977) Studies on the regulation of lymphocyte reactivity by normal and activated macrophages. Cell Immunol 30:108
Wood GW, Neff JE, Stephens R (1979) Relationship between monocytosis and T-lymphocyte function in human cancer. J Natl Cancer Inst 63:587
Zembala M, Mytar B, Popiela T, Asherson GL (1977) Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: the role of suppressor cells. Int J Cancer 19:605
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vose, B.M., Moore, M. Heterogeneity of suppressors of mitogen responsiveness in human malignancy. Cancer Immunol Immunother 9, 163–171 (1980). https://doi.org/10.1007/BF00205621
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205621