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Immune infiltrates and cytokines in gliomas

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Summary

Frozen sections of 21 gliomas were analysed to characterize inflammatory infiltrating cells, HLA-DR antigen expression and cytokine secretion. Mononuclear cells infiltrating the tumours were mostly macrophages, which were detected in 100% of cases, and expressed HLA-DR antigens. Lymphocytes were less frequently seen and expressed the CD8 phenotype.

Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6), two cytokines mainly produced by activated cells of the macrophage lineage, were demonstrated expecially in neoplastic astrocytes. IL-1β immunoreactivity was detected in all tumours, and was prevalent in more anaplastic gliomas; IL-6 was found in anaplastic gliomas and in glioblastomas. IL-1 receptors were expressed by both infiltrating macrophages and neoplastic astrocytes in the gliomas analysed. These findings suggest that cytokine production in gliomas seems not related to immune reactions against the tumour and their synthesis by anaplastic astrocytes could follow an unregulated activation of many metabolic processes after neoplastic transformation.

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References

  1. Bodmer S, Strommer K, Frei K, Siepl C, De Tribolet N, Heid I, Fontana A (1989) Immunosuppression and transforming growth factor-β in glioblastoma. Preferential production of transforming growth factor-β-2. J Immunol 143: 3222–3229

    PubMed  Google Scholar 

  2. Burger PC, Vogel FS, Green SB, Strike TA (1985) Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer 56: 1106–1111

    PubMed  Google Scholar 

  3. Esiri MM, McGree JOD (1986) Monoclonal antibody to macrophages (EBM/11) labels macrophages and microglial cells in human brain. J Clin Pathol 39: 615–621

    PubMed  Google Scholar 

  4. Fontana A, Hengartner H, De Tribolet N, Weber E (1984) Glioblastoma cells release interleukin-1 and factors inhibiting interleukin-2 mediated effects. J Immunol 132: 1837–1842

    PubMed  Google Scholar 

  5. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A (1989) On the cellular source and function of Interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol 19: 689–694

    PubMed  Google Scholar 

  6. Gately MK, Glaser M, McCarron RM, Dick SJ, Dick MD, Mettetal RW, Kornblith PL (1982) Mechanisms by which human gliomas may escape cellular immune attack. Acta Neurochir (Wien) 64: 175–197

    Google Scholar 

  7. Giometto B, Bozza F, Argentiero V, Gallo P, Pagni S, Piccinno MG, Tavolato B (1990) Transferrin receptors in rat central nervous system. An immunocytochemical study. J Neurol Sci 98: 81–90

    PubMed  Google Scholar 

  8. Giulian D, Lachman LB (1985) Interleukin-1 stimulates astroglial proliferation after brain injury. Science 228: 497–499

    PubMed  Google Scholar 

  9. Graves DT, Jiang YL, Williamson MJ, Valente AJ (1989) Identification of monocyte chemotactic activity produced by malignant cells. Science 245: 1490–1493

    PubMed  Google Scholar 

  10. Griffin WST, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White L, Araoz C (1989) Brain Interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86: 7611–7615

    PubMed  Google Scholar 

  11. Hitchcock ER, Morris CS (1988) Mononuclear cell infiltrate in central portions of human astrocytomas. J Neurosurg 68: 432–437

    PubMed  Google Scholar 

  12. Kawano M, Hirano T, Matsuda P, Taga T, Hurii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanale H, Kuramoto A, Kishimoto T (1988) Autocrine generation and essential requirement of BSF-23/IL-6 for human multiple myelomas. Nature 332: 83–85

    PubMed  Google Scholar 

  13. Kril MP, Apuzzo MLJ (1983) Observations in the study of T lymphocyte subsets by monoclonal antibodies and flow cytometric analysis in intracranial neoplastic disorders. Clin Neurosurg 30: 125–136

    PubMed  Google Scholar 

  14. Jablons DM, McIntosh JK, Mule JJ, Nordan RP, Rudikoff S, Lotze MT (1989) Induction of Interferon B-2/Interleukin-6 (IL-6) by cytokine administration and detection of circulating interleukin-6 in tumor bearing state. Ann NY Acad Sci 557: 157–161

    PubMed  Google Scholar 

  15. Leppert D, Frei K, Gallo P, Yasargil MG, Hess H, Baumgartner G, Fontana A (1989) Brain tumours: detection of B-cell stimulatory factor-2/interleukin-6 in the absence of oligoclonal bands of immunoglobulins. J Neuroimmunol 24: 259–264

    PubMed  Google Scholar 

  16. Lichtor T, Dohrmann GJ, Gurney ME (1990) Cytokine gene expression by human gliomas. Neurosurgery 26: 788–792

    PubMed  Google Scholar 

  17. Merlo A, Juretic A, Zuber M, Filgueira L, Luscher U, Caetano V, Ulrich J, Gratzl O, Heberer M, Spagnoli GC (1993) Cytokine gene expression in primary brain tumors, metastases and meningiomas suggests specific transcription patterns. Eur J Cancer 29: 2118–2225

    Google Scholar 

  18. Miescher S, Whiteside TL, De Tribolet N, Fliender VV (1988) In situ characterization, clonogenic potential, and antitumor cytolytic activity of T lymphocytes infiltrating human brain cancers. J Neurosurg 68: 438–448

    PubMed  Google Scholar 

  19. Morantz RA, Wood GW, Foster M, Clark M, Gollahon K (1979) Macrophages in experimental and human tumors. Part 2: studies of the macrophage content of human brain tumors. J Neurosurg 50: 305–311

    PubMed  Google Scholar 

  20. Morimura T, Neuchrist C, Kitz K, Budka H, Schemer O, Kraft D, Lassman H (1990) Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol 80: 287–294

    PubMed  Google Scholar 

  21. Morris CS, Esiri MM (1991) Immunocytochemical study of macrophages and microglial cells and extracellular matrix components in human CNS diseases. Gliomas. J Neurol Sci 101: 47–58

    PubMed  Google Scholar 

  22. Paine JT, Handa H, Yamasaki T, Yamashita J, Miyatake S (1986) Immunohistochemical analysis of infiltrating lymphocytes in central nervous system tumors. Neurosurgery 18: 776–782

    Google Scholar 

  23. Ridley A, Cavanagh JB (1971) Lymphocytic infiltration in gliomas: evidence of possible host resistence. Brain 94: 117–124

    PubMed  Google Scholar 

  24. Rossi ML, Hughes JT, Esiri MM, Coakham HB, Brownell DB (1987) Immunohistochemical study of mononuclear cell infiltrate in malignant gliomas. Acta Neuropathol 74: 269–277

    PubMed  Google Scholar 

  25. Rossi ML, Cruz-Sanchez FF, Hughes JT, Esiri MM, Coakham HB, Moss TH (1988) Mononuclear cell infiltrate and HLA-DR expression in low grade astrocytomas: an immunohistochemical study of 23 cases. Acta Neuropathol 76: 281–286

    PubMed  Google Scholar 

  26. Schackert G, Simmons RS, Buzbee TM, Hume DA, Fidler IJ (1988) Macrophage infiltration into experimental brain metastases: occurrence through an intact blood-brain barrier. J Natl Cancer 80: 1027–1034

    Google Scholar 

  27. Schiffer D, Croveri G, Pautasso C (1974) Frequenza e significato degli infiltrati linfo-plasmacellulari nei gliomi umani. Tumori 60: 177–184

    PubMed  Google Scholar 

  28. Shinonaga M, Cheng Chang C, Suzuki N, Sato M, Kuwabara T (1988) Immunohistological evaluation of macrophage infiltrates in brain tumors. J Neurosurg 68: 259–265

    PubMed  Google Scholar 

  29. Tabibzadeh SS, Poubouridis D, May LT, Sehgal PB (1989) Interleukin-6 immunoreactivity in human tumors. Am J Pathol 135: 427–433

    PubMed  Google Scholar 

  30. Thompson DK, Haddow JE, Smith DE, Ritchie RF (1983) Elevated serum acute phase protein levels as predicators of disseminated breast cancer. Cancer 51: 2100–2104

    PubMed  Google Scholar 

  31. Van Meier E, Sawamura Y, Diserens AC, Hamou MF, De Tribolet N (1990) Human glioblastoma cells release Interleukin 6 in vivo and in vitro. Cancer Res 50: 6683–6688

    PubMed  Google Scholar 

  32. Von Hanwehr RI, Hoffman FM, Taylor CR, Apuzzo MLJ (1984) Mononuclear lymphoid populations infiltrating the microenvironment of the primary CNS tumors. Characterization of cell subsets with monoclonal antibodies. J Neurosurg 60: 1138–1147

    PubMed  Google Scholar 

  33. Vose BM, Moore M (1985) Human tumor-infiltrating lymphocytes: a marker of host response. Semin Hematol 22: 27–40

    PubMed  Google Scholar 

  34. Yasukawa K, Hirano T, Watanabe Y, Murateni K, Matsuda T, Nakai S, Kishimoto LT (1987) Structure and expression of human B cell stimulatory factor-2 (BSF-2/TL-6) gene. EMBO J 6: 2939–2945

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Neurology Second Clinic, University of Padua, School of Medicine, Padova, Italy

    B. Giometto, F. Bozza, F. Faresin, L. Alessio, S. Mingrino & B. Tavolato

  2. Division of Neurosurgery, University of Padua, School of Medicine, Padova, Italy

    L. Alessio, S. Mingrino & B. Tavolato

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  1. B. Giometto
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  2. F. Bozza
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  3. F. Faresin
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  4. L. Alessio
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  5. S. Mingrino
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  6. B. Tavolato
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Giometto, B., Bozza, F., Faresin, F. et al. Immune infiltrates and cytokines in gliomas. Acta neurochir 138, 50–56 (1996). https://doi.org/10.1007/BF01411724

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