Skip to main content
SpringerLink
Log in

Monocyte tumoricidal activity and tumor necrosis factor production in patients with malignant brain tumors

  • Original articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Monocyte-mediated tumoricidal activity, tumor necrosis factor α (TNFα) secretion and gene expression were examined in astrocytoma patients, patients with other types of brain tumors (primary or metastatic), and normal individuals. The spontaneous monocyte-mediated tumoricidal activity of either patient group against an astrocytoma cell line was significantly greater than normal. There was no difference between patient groups. When monocytes were stimulated with lipopolysaccharide in vitro, tumoricidal activity increased in all patient groups. Patient monocyte activity tested shortly (48 h) after surgery was not different from that before surgery. Both spontaneous and stimulated monocyte cytocidal activities were tumor-cell-restricted: melanoma and astrocytoma cells were equally susceptible but non-neoplastic glial cells were not affected. Examination of monocyte TNFα secretion and mRNA expression indicated that patient activity was comparable to or greater than normal. These results demonstrate that, despite steroid therapy, circulating monocytes in astrocytoma and other brain tumor patients retain intact functional activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barna BP, James K, Deodhar SD (1987) Activation of human monocyte tumoricidal activity by C-reactive protein. Cancer Res 47: 3959

    Google Scholar 

  2. Barna BP, Estes ML, Jacobs BS, Hudson S, Ransohoff RM (1990) Human astrocytes proliferate in response to tumor necrosis factor alpha. J Neuroimmunol 30: 239

    Google Scholar 

  3. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami C (1986) Control of cachectin (tumor necrosis factor) synthesis: Mechanisms of endotoxin resistance. Science 232: 977

    Google Scholar 

  4. Braun DP, Penn RD, Flannery AM, Harris JE (1982) Immunoregulatory cell function in peripheral blood leukocytes of patients with intracranial gliomas. Neurosurgery 10: 203

    Google Scholar 

  5. Brooks EL, Roszman T (1987) Role of interleukin-2 (IL-2) and IL-2 receptor expression in the proliferative defect observed in mitogenstimulated lymphocytes from patients with gliomas. J Natl Cancer Inst 78: 919

    Google Scholar 

  6. Brooks WH, Netsky MG, Normansell DE, Horwitz DA (1972) Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor. J Exp Med 136: 1631

    Google Scholar 

  7. Chomczynski P, Sacchi M (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156

    Google Scholar 

  8. Cleveland DW, Lopata MA, McDonald RJ, Cowan NJ, Ruther WJ, Kirschner M (1980) Number and evolutionary conservation of a- and b-tubulin and b- and g-actin genes using specific cloned cDNA probes. Cell 20: 95

    Google Scholar 

  9. Dimitriu-Bona A, Burmester GR, Waters SJ, Winchester RJ (1983) Human mononuclear phagocyte differentiation antigens: I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol 130: 145

    Google Scholar 

  10. Feinman R, Henriksen-DeStefano D, Tsujimoto M, Vilcek J (1987) Tumor necrosis factor is an important mediator of tumor cell killing by human monocytes. J Immunol 138: 635

    Google Scholar 

  11. Fontana A, Hengartner H, de Tribolet N, Weber E (1984) Glioblastoma cell release interleukin-1 and factors inhibiting interleukin-2-mediated effects. J Immunol 132: 1837

    Google Scholar 

  12. Hogan MM, Vogel SN (1988) Inhibition of macrophage tumoricidal activity by glucocorticoids. J Immunol 140: 513

    Google Scholar 

  13. Kleinerman ES, Herberman RB (1984) Tumoricidal activity of human monocytes: evidence for cytolytic function distinct from that of NK cells. J Immunol 133: 4

    Google Scholar 

  14. Kuppner MC, Hamou MF, Bodmer S, Fontana A, de Tribolet N (1988) The glioblastoma-derived T-cell suppressor factor/transforming growth factor beta 2 inhibits the generation of lymphokine-activated killer (LAK) cells. Int J Cancer 42: 562

    Google Scholar 

  15. Lachman LB, Brown DC, Dinarello CA (1987) Growth-promoting effect of recombinant interleukin 1 and tumor necrosis factor for a human astrocytoma cell line. J Immunol 138: 2913

    Google Scholar 

  16. Maniatis T, Fritsch EF, Sambrook J (1989) Molecular cloning: A laboratory manual, 2nd edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

    Google Scholar 

  17. Miescher S, Whiteside TL, de Tribolet N, von Fliedner F (1988) In situ characterization, clonogenic potential, and antitumor cytolytic activity of T lymphocytes infiltrating human brain cancers. J Neurosurg 68: 434

    Google Scholar 

  18. Morantz RA, Wood GW, Foster M, Clark M, Gollahon K (1979) Macrophages in experimental and human brain tumors: part 2. Studies of the macrophage content of human brain tumors. J Neurosurg 50: 305

    Google Scholar 

  19. Pennica D, Nedwin GE, Hayflick JS, Secburgh PH, Deryck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV (1984) Human tumor necrosis factor: Precursor structure expression and homology to lymphotoxin. Nature 312: 724

    Google Scholar 

  20. Shapiro WR (1982) Treatment of neuroectodermal brain tumors. Ann Neurol 12: 231

    Google Scholar 

  21. Strieter RM, Remick DG, Lynch JP, Genord M, Raidord C, Spengler R, Kunkel SL (1989) Differential regulation of tumor necrosis factor-alpha in human alveolar macrophages and peripheral blood monocytes: a cellular and molecular analysis. Am J Resp Cell Mol Biol 1: 57

    Google Scholar 

  22. Thomassen MJ, Barna BP, Rankin D, Wiedemann HP, Ahmad M (1989) Differential effect of recombinant granulocyte macrophage colony-stimulating factor on human monocytes and alveolar macrophages. Cancer Res 49: 4086

    Google Scholar 

  23. Thomassen MJ, Ahmad M, Barna BP, Antal J, Wiedemann HP, Meeker DP, Klein J, Bauer L, Gibson V, Andresen S, Bukowski RM (1991) Induction of cytokine mRNA and secretion in alveolar macrophages and blood monocytes from patients with lung cancer receiving GM-CSF therapy. Cancer Res 51: 857

    Google Scholar 

  24. Walker MD, Green SB, Byar DP, Alexander E, Batzdorf U, Brooks W, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J II, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA (1980) Randomized comparisons of the radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303: 1323

    Google Scholar 

  25. Whiteside TL, Wang YL, Selker RG, Herberman RB (1988) In vitro generation and antitumor activity of adherent lymphokine-activated killer cells from the blood of patients with brain tumors. Cancer Res 48: 6069

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Immunopathology, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, 44195-5131, Cleveland, OH, USA

    Barbara P. Barna

  2. Department of Neurology, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, 44195-5131, Cleveland, OH, USA

    Lisa R. Rogers

  3. Department of The Research Institute, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, 44195-5131, Cleveland, OH, USA

    Mary Jane Thomassen

  4. Department of Neurosurgery, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, 44195-5131, Cleveland, OH, USA

    Gene H. Barnett

  5. Department of Pathology, The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, 44195-5131, Cleveland, OH, USA

    Melinda L. Estes

Authors
  1. Barbara P. Barna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa R. Rogers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mary Jane Thomassen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gene H. Barnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Melinda L. Estes
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by grant CA-49 950 from the National Cancer Institute (B.P.B) and grant 1454-HL from the National Institutes of Health (M.L.E.)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barna, B.P., Rogers, L.R., Thomassen, M.J. et al. Monocyte tumoricidal activity and tumor necrosis factor production in patients with malignant brain tumors. Cancer Immunol Immunother 33, 314–318 (1991). https://doi.org/10.1007/BF01756596

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01756596

Key words

Search

Navigation