Abstract
Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with Interleukin-2 (ILr2) or a glucomannan-protein antigen of Candida albicans (GMP) then assayed for proliferation, production of IFN-gamma, and generation of cytotoxic effectors against either K562 tumor cell line or freshly-cultured allogenic glioma cells. PBMC of healthy, age and sex-matched subjects were the controls. PBMC of glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a lesser ability to produce IFN as well as a substantial inability to generate cytotoxic effectors following GMP stimulation. PBMC of glioma patients were fully responsive to ILr2 in cytotoxicity generation, as were the PBMC from normal subjects. The results suggest that glioma patients may have a defective antigen-mediated activation of natural cytotoxic effectors. This hyporesponsiveness is not accompanied by depressed lymphoproliferation and does not apparently involve a reduced response to IL-2.
Similar content being viewed by others
References
Ommaya AK: Immunotherapy of gliomas: a review. Adv Neurol 15:337–354, 1986
Terry WD, Rosemberg SA (eds): Immunotherapy of human cancer. Elsevier/North-Holland, New York, 1982
Brooks WH, Caldwell HD, Mortara RH: Immune responses in patients with glioma. Surg Neurol 2:419–423, 1974
Mahaley MS, Brooks WH, Roszman TL, Bigner DD, Dudka L, Richardson S: Immunobiology of primary intracranial tumors. Part I: Studies of cellular and Immoral general immune competence of brain-tumor patients. J Neurosurg 44:467–479, 1977
Blomgren H, Blom U, Ullen H: Relation between the site of primary intracranial tumors and mitogenic responses of blood lymphocytes. Cancer Immunol Immunother 21:31–38, 1986
Roszman TL, Brooks WH, Elliott LH: Immunobiology of primary intracranial tumors. VI Suppressor cell function and lectin-binding lymphocyte subpopulations in patients with cerebral tumors. Cancer 50:1273–1279, 1982
Brooks WH, Netsky MG, Normansell DE, Horwitz DA: Depressed cell-mediated immunity in patients with primary intracranial tumors. J Exp Med 136:1631–1647, 1972
Neuwelt EA, Kikuchi K, Hill S, Lipsky P, Frenkel EP: Immune responses in patients with brain tumors: factors such as anticonvulsants that may contribute to impaired cell-mediated immunity. Cancer 51:248–255, 1983
Rosemberg S: Lymphokine-activated killer cells: a new approach to immunotherapy of cancer. JNCI 75:595–603, 1985
Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA: In vitro killing of human glioblastoma by interleukin-2-activated autologous lymphocytes. J Neurosurg 64:114–117, 1986
Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA: Interleukin-2 and autologous lymphokine-activated killer cells in the treatment of malignant glioma. J Neurosurg 64:743–749, 1986
Ausiello C, Spagnoli GC, Boccanera M, Casalinuovo I, Malavasi F, Casciani CU, Cassone A: Proliferation of human peripheral blood mononuclear cells induced by Candida albicans and its cell wall fractions. J Med Microbiol 22:195–202, 1986
Spagnoli GC, Ausiello C, Casalinuovo I, Antonelli G, Dianzani F, Cassone A: Candida albicans and a phosphorylated glucomannan-protein fraction of its cell wall induce production of immune interferon by human peripheral blood mononuclear cells. IRCS Med Sci 13:1190–1191, 1985
Ausiello C, Spagnoli GC, Antonelli G, Malavasi F, Dianzani F, Casciani CU, Cassone A: Generation and characterization of cytotoxic activity against tumor cells stimulated in vitro by a glucomannan-protein preparation of Candida albicans. J Biol Reg Homeost Agents 1:59–68, 1987
Cassone A, Marconi P, Bistoni F, Baccarini M, Garaci E, Mattia E, Bonmassar E: Immunoadjuvant effects of Candida albicans and its cell wall fractions in a mouse lymphoma model. Cancer Immunol Immunother 10:181–190, 1981
Lauro GM, Di Lorenzo N, Grassi M, Maleci A, Guidetti B: Prostaglandin EZ as an immunomodulating factor released in vitro by human glioma cells. Acta Neuropathol 69:278–282, 1986
Ausiello C, Sorrentino V, Ruggiero V, Rossi GB: Action of lysosomatropic amines on spontaneous and interferon-enhanced NK and CTL cytolysis. Immunol Lett 8:11–15, 1984
Stanton GJ, Langford MJ, Dianzani F: Virus yield reduction assay for interferon by titration of Sindbis virus hemagglutinin. Methods Enzymol 78:351–357, 1981
Dianzani F, Monahan TM, Slupham A, Zucca M: Enzymatic induction of interferon production by galactose oxidase treatment of human lymphoid cells. Infect Immun 26:879–882, 1979
Dianzani F, Ramenghi U, Santiano M, Capobianchi MR, Antonelli G: Membrane events leading to interferon-induction by antigens. Proc Soc Exp Biol Med 178:139–142, 1985
Herberman HB: Interferon and cytotoxin effector cells. In: Vilcek J and De Maeyer E (eds). Interferon and immune system. Elsevier-Amsterdam, 1984, pp 61–84.
Fontana A, Hengartener H, De Tribolet N, Weber E: Glioblastoma cells release interleukin 1 and factors inhibiting interleukin-2 mediated effects. J Immunol 132:1837–1846, 1984
Schwyzer M, Fontana A: Partial purification and biochemical characterization of a T cell suppressor factor produced by human glioblastoma cells. J Immunol 134:1003–1009, 1985
Tartof D, Check IJ, Matutis A, Hunter RL, Fitch FW. Studies on stimulation of cell-mediated cytotoxicity by skin test antigens. J Immunol 125:2790–2796, 1980
Tartof D, Curran JS, Levitt D, Loken MR: The skin test antigen stimulated killer (STAK) cell mediating NK-like CMC is OKMI positive and OKT3 negative. Clin Exp Immunol 54:561–566, 1983
Ullen H, Blom U, Blomgren H: Natural killer activity of blood lymphocytes in patients with primary intracranial tumors. Correlation of histological tumor type and anatomical site. Eur J Cancer Clin Oncol 10:1239–1245, 1986
Hahn BH, MacDermott RP, Pletscher SB, Jacobs LS, Beale MG: Immunosuppressive effects of low doses of glucocorticoids: Effects on autologous and allogenic mixed leukocyte reactions. J Immunol 127:2812–2817, 1980
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ausielloh, C., Maleci, A., Spagnolil, G.C. et al. Cell-mediated cytotoxicity in glioma-bearing patients: Differential responses of peripheral blood mononuclear cells to stimulation with interleukin-2 and microbial antigen. J Neuro-Oncol 6, 329–338 (1988). https://doi.org/10.1007/BF00177428
Issue Date:
DOI: https://doi.org/10.1007/BF00177428