Advertisement

Acta Neuropathologica

, Volume 74, Issue 3, pp 269–277 | Cite as

Immunohistological study of mononuclear cell infiltrate in malignant gliomas

  • M. L. Rossi
  • J. T. Hughes
  • M. M. Esiri
  • H. B. Coakham
  • D. B. Brownell
Regular Papers

Summary

Sixty-five malignant gliomas (astrocytomas grade 3 and 4 and glioblastomas) were examined by means of immunoperoxidase staining on frozen tissue using various monoclonal antibodies directed against macrophages, lymphocytes and natural killer cells. Depending on the antibody used, the presence of macrophages in tumours ranged from 85%–100%. Many of the tumours contained substantial numbers of macrophages not only, as expected, in necrotic areas but also in intact tumour tissue. Eighty-nine percent of 39 tumours tested contained Fc receptorbearing mononuclear cells in viable tumour. In 100% of 44 tumours tested for HLADR class 2 major histocompatibility complex antigen this antigen was detected in the macrophages. In 40% of these 44 cases, HLADR antigen was also present on the tumour cells. Eighty-eight percent of 53 tumours tested contained T cells in viable tumour and the majority of these cells were T cytotoxic/suppressor (T8). Twenty-four percent of 33 tumours contained no T helper/inducer (T4) lymphocytes and in the other 76% there were few positive cells. Only 9% of 21 tumours contained natural killer cells (NK). B cells were absent from 88% of 61 tumours and almost all of the remainder contained only a small number of B cells. The findings are discussed with reference to a possible host immune response to gliomas and relevant literature is reviewed.

Key words

Glioma Macrophage Lymphocyte Cellular immunity Major histocompatibility complex antigens 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Alexander P (1976) The functions of the macrophages in malignant disease. Annu Rev Med 27:207–224Google Scholar
  2. 2.
    Basham T, Merrigan TC (1982) Immunoregulation by Y interferon? Nature 299:278Google Scholar
  3. 3.
    Bertrand I, Mannen H (1960) Études des réactions vasculairés dans les astrocytomes. Rev Neurol (Paris) 102:3–19Google Scholar
  4. 4.
    Brooks WH, Markesbery WR, Gupta GD, Roszman TL (1978) Relationship of lymphocyte invasion and survival of brain tumour patients. Ann Neurol 4:219–224Google Scholar
  5. 5.
    Carrel S, De Tribolet N, Gross N (1982) Expression of HLADR and common acute lymphoblastic lukemia antigen on glioma cells. Eur J Immunol 12:354–357Google Scholar
  6. 6.
    Clarkson S, Kimberley RP, Valinsky JE, Witmer M, Bussel JB, Nachman RL, Unkeless JC (1986) Blockade of clearance of immmune complexes by anti-Fcy receptor monoclonal antibody. J Exp Med 164:474–489Google Scholar
  7. 7.
    Coakham HB, Garson JA, Brownell B, Kemshead JT (1985) Diganosis of cerebral neoplasms using monoclonal antibodies. Prog Exp Tumor Res 29:55–77Google Scholar
  8. 8.
    Esiri MM, McGee J O'D (1986) Monoclonal antibody to macrophages (EBM11) labels macrophages and microglial cells in human brain. J Clin Pathol 39:615–621Google Scholar
  9. 9.
    Farrar WL, Johnson HM, Farrar J (1981) Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin-2. J Immunol 126:1120–1125Google Scholar
  10. 10.
    Fleit HB, Wirght SD, Unkeless JC (1982) Human neutrophil Fcy receptor distribution and structure. Proc Natl Acad Sci USA 79:3275–3279Google Scholar
  11. 11.
    Fontana A, Fierz W, Wekerle H (1984) Astrocytes present myelin basic protein to encephalogenic T cell lines. Nature 307:273–276Google Scholar
  12. 12.
    Friedman RM, Vogel SN (1983) Interferon with special emphasis on the immune system. Adv Immunol 34:97–100Google Scholar
  13. 13.
    Gillis S, Smith KA (1977) Long term culture of tumour specific cytotoxic T cells. Nature 268:154–156Google Scholar
  14. 14.
    Henney CS, Kuribayashi K, Kern DE, Gillis S (1981) Interleukin-2 augments natural killer cell activity. Nature 291:335–338Google Scholar
  15. 15.
    Hofman FM, Von Hanwer RI, Dinarello CA, Mizel SB, Hinton D, Merrill J (1986) Immunoregulatory molecules and interleukin-2 receptor identified in multiple sclerosis brain. J Immunol 136:3239–3245Google Scholar
  16. 16.
    Hogg N (1986) Factor-induced differentiation and activation of macrophages. Immunol Today 7:65–66Google Scholar
  17. 17.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA (1986) Interleukin-2 or autologous lymphokine activated killer cell treatment of malignant gliomas. Cancer Res 46:2101–2104Google Scholar
  18. 18.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA (1986) In vitro killing of human glioblastoma by interleukin-2 activated autologous lymphocytes. J Neurosurg 64:114–117Google Scholar
  19. 19.
    Kernohan JW, Mabon RF, Stein JH, Adson AW (1949) A simplified classification of the gliomas. Proc Staff Meet Mayo Clin 24:71–75Google Scholar
  20. 20.
    King DP, Jones PP (1983) Induction of Ia and H-2 antigens on a macrophage cell line by immune interferon. J Immunol 131:315–318Google Scholar
  21. 21.
    Kril MP, Apuzzo MLJ (1983) Observation in the study of T lymphocyte subsets by monoclonal antibodies and flow cytometric analysis in intracranial neoplastic disorders. Clin Neurosurg 30:125–136Google Scholar
  22. 22.
    Lampson LA, Hickey WF (1986) Monoclonal antibody analysis of MHC expression in human brain biopsies: tissue ranging from histologically normal to that showing different levels of glial tumour involvement. J Immunol 136:4054–4062Google Scholar
  23. 23.
    Matthews N (1981) Production of anti-tumour cytotoxin by human monocytes. Immunology 44:135–142Google Scholar
  24. 24.
    McKinnon KP, Chen AR, Argov S, Love B, Koren HS (1986) Cytolysis of actinomycin-d-treated target cells by cell-free supernatants from human monocytes. Immunobiology 171:26–44Google Scholar
  25. 25.
    Morantz RA, Wood GW, Foster M, Clark M, Gollahon K (1979) Macrophages in experimental and human tumours. Studies of the macrophage content of human brain tumours. J Neurosurg 50:305–311Google Scholar
  26. 26.
    Mørk SJ, Nyland H, Matre R, Ganz J (1985) Characterization of host mononuclear cells in gliomas. J Neuropathol Exp Neurol 44:317 (abstr)Google Scholar
  27. 27.
    Mule J, Shu S, Rosenberg SA (1985) The anti-tumour effect of lymphokine-activated killer cells and recombinant interleukin-2 in vivo. J Immunol 135:646–652Google Scholar
  28. 28.
    Palma L, Di Lorenzo N, Guidetti B (1978) Lymphocytic infiltrates in primary glioblastomas and recidivous gliomas: incidence, fate and relevance to prognosis in 228 operated cases. J Neurosurg 49:854–861Google Scholar
  29. 29.
    Philip R, Epstein LB (1986) Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, Y interferon and interleukin-1. Nature 323:86–89Google Scholar
  30. 30.
    Phillips JP, Eremin O, Anderson JR (1982) Lymphoreticular cells in human brain tumours and in normal brain. Br J Cancer 45:61–69Google Scholar
  31. 31.
    Rayner AA, Grimm EA, Lotze MT, Wilson DJ, Rosenberg SA (1985) Lymphokine-activated killer cell phenomenon. IV. Lysis by LAK cell clones of fresh human tumour cells from autologous and multiple allogeneic tumours. JNCl 75:67–75Google Scholar
  32. 32.
    Ridley A, Cavanagh JB (1971) Lymphocytic infiltration in gliomas: evidence of possible host resistance. Brain 94:117–124Google Scholar
  33. 33.
    Rosenberg SA, Lotze MT, Muul L, Leitman S, Chang A, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492Google Scholar
  34. 34.
    Schiffer D, Croveri G, Pautasso C (1974) Frequenza e significato degli infiltrati linfo-plasmacellulari nei gliomi umani. Tumori 60:177–184Google Scholar
  35. 35.
    Stavrou D, Anzil AP, Weidenbach W, Rodt H (1977) Immunofluorescence study of lymphocytic infiltration in gliomas. Identification of T lymphocytes. J Neurol Sci 33:275–282Google Scholar
  36. 36.
    Steeg PS, Moore RN, Johnson H, Oppenheim J (1982) Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity. J Exp Med 156:1780–1793Google Scholar
  37. 37.
    Takeuchi J, Barnard RO (1976) Perivascular lymphocytic cuffing in astrocytomas. Acta Neuropathol (Berl) 35:265–271Google Scholar
  38. 38.
    Traugott U, Scheinberg LC, Raine CS (1985) On the presence of Ia-positive endothelial cells and astrocytes in multiple sclerosis and its relevance to antigen presentation. J Neuroimmunol 8:1–14Google Scholar
  39. 39.
    Volc-Platzer B, Majdic O, Knapp W, Wolff K, Hinterberger W, Lechner K, Stingl G (1984) Evidence of HLADR antigen biosynthesis in human keratinocytes in disease. J Exp Med 159:1784–1789Google Scholar
  40. 40.
    Von Hanwehr RI, Hofman FM, Taylor CR, Apuzzo MLJ (1984) Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumours. Characterisation of cell subsets with monoclonal antibodies. J Neurosurg 60:1138–1147Google Scholar
  41. 41.
    Werdelin O, Schevach M (1979) Role of nominal antigen and Ia antigen in the binding of antigen-specific T lymphocytes to macrophages. J Immunol 123:2779–2783Google Scholar
  42. 42.
    Wood GW, Morantz RA (1979) Immunohistological evaluation of the lymphoreticular infiltrate in human CNS tumours. JNCI 62:485–490Google Scholar
  43. 43.
    Woodrofe MN, Bellamy AS, Feldman M, Davison AN, Cuzner ML (1987) Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis: possible role of microglia in lesion growth. J Neurol Sci 74:135–152Google Scholar
  44. 44.
    Yu DTY, Fu SM, Winchester J, Hunkel HG (1980) Two types of Ia-positive cells. Synthesis and exchange of Ia antigens. J Exp Med 152:89s-98sGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • M. L. Rossi
    • 1
  • J. T. Hughes
    • 1
  • M. M. Esiri
    • 1
  • H. B. Coakham
    • 2
  • D. B. Brownell
    • 2
  1. 1.Department of NeuropathologyThe Radcliffe InfirmaryOxfordUK
  2. 2.Department of Neurosurgery and NeuropathologyFrenchay HospitalBristolUK

Personalised recommendations