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Mechanisms by which human gliomas may escape cellular immune attack

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Summary

Whereas substantial evidence indicates that the majority of glioma patients make humoral immune responses to their own tumours, the evidence that glioma patients make significant cellular immune responses is more tenuous and controversial. In order to study those properties of human gliomas that might contribute to their ability to escape cell-mediated immune attack, we have examined the ability of cultured human glioma cells to elicit allogeneic cytolytic lymphocyte responses in vitro. Five of ten glioma lines were unable to elicit allogeneic cytolytic lymphocyte responses in mixed lymphocyte-tumour cultures, despite the presence of serologically detectable alloantigens on the surface of the glioma cells. Analysis of the reasons why certain glioma lines failed to stimulate cytolytic lymphocyte responses revealed three distinct mechanisms by which human gliomas may escape cellular immune attack: 1. a defect in immunogenicity which can be overcome by “help” from an allogeneic mixed lymphocyte reaction, 2. the secretion of a protective mucopolysaccharide coat, and 3. the production of macromolecular immunosuppressive substance(s). The implications of these findings for the immunotherapy of human gliomas are discussed.

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Abbreviations

CTL:

cytolytic T lymphocyte

C:

complement

FBS:

foetal bovine serum

MLR:

mixed lymphocyte reaction

MLTC:

mixed lymphocyte tumour culture

NK:

natural killer

PBS:

phosphate-buffered saline

R:

responder lymphocyte

S:

stimulator lymphocyte

TCGF:

T cell growth factor

TCM:

tissue culture medium

References

  1. Anderson, D. R., Spencer, W. H., Ultrastructural and histochemical observations of optic nerve gliomas. Arch. Ophthal.83 (1970), 324–335.

    PubMed  Google Scholar 

  2. Anderson, R. J., McBride, C. M., Hersh, E. M., Lymphocyte blastogenic responses to cultured allogenic tumor cells in vitro. Cancer Res.32 (1972), 988–992.

    PubMed  Google Scholar 

  3. Apuzzo, M. L. J., Mitchell, M. S., Immunological aspects of intrinsic glial tumors. J. Neurosurg.55 (1981), 1–18.

    PubMed  Google Scholar 

  4. Arseni, C., Carp, N., Mestes, E., Adel, M., Histochemistry of mucopoly-saccharides in brain tumors. Acta Neuropathol. (Berl.)7 (1967), 275–284.

    Google Scholar 

  5. Bach, F. H., Bach, M. L., Sondel, P. M., Differential function of major histocompatibility complex antigens in T-lymphocyte activation. Nature259 (1976), 273–281.

    PubMed  Google Scholar 

  6. Bach, F. H., Grillot-Courvalin, C., Kuperman, O. J., Sollinger, H. W., Hayes, C., Sondel, P. M., Alter, B. J., Bach, M. L., Antigenic requirements for triggering of cytotoxic T lymphocytes. Immunol. Rev.35 (1977), 76–96.

    PubMed  Google Scholar 

  7. Bloom, H. J. G., Peckham, M. J., Richardson, A. E., Alexander, P. A., Payne, P. M., Glioblastoma multiforme: A controlled trial to assess the value of specific active immunotherapy in patients treated by radical surgery and radiotherapy. Brit. J. Cancer27 (1973), 253–267.

    PubMed  Google Scholar 

  8. Bolhuis, R. L. H., Schellekens, H., Induction of natural killer cell activity and allocytotoxicity in human peripheral blood lymphocytes after mixed lymphocyte culture. Scand. J. Immunol.13 (1981), 401–412.

    PubMed  Google Scholar 

  9. Boyum, A., Isolation of mononuclear cells and granulocytes from human blood. Scand. J. Clin. Lab. Invest.21 (Suppl. 97) (1968), 77–89.

    PubMed  Google Scholar 

  10. Brooks, W. H., Latta, R. B., Mahaley, M. S., Roszman, T. L., Dudka, L., Skaggs, C., Immunobiology of primary intracranial tumors. Part 5: Correlation of a lymphocyte index and clinical status. J. Neurosurg.54 (1981), 331–337.

    PubMed  Google Scholar 

  11. Brooks, W. H., Netsky, M. G., Normanseil, D. E., Horwitz, D. E., Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor. J. Exp. Med.136 (1972), 1631–1647.

    PubMed  Google Scholar 

  12. Goakham, H. B., Kornblith, P. L., Quindlen, E. A., Pollock, L. A., Wood, W. C., Hartnett, L. C., Autologous humoral response to human gliomas and analysis of certain cell surface antigens: in vitro study with the use of microcytotoxicity and immune adherence assays. J. Natl. Cancer Inst.64 (1980), 223–233.

    PubMed  Google Scholar 

  13. Dohan, F. C., Kornblith, P. L., Wellum, G. R., Pfeiffer, S. F., Levine, L., S-100 protein and 2′, 3′-cyclic nucleotide 3′-phospho-hydrolase in human brain tumors. Acta Neuropathol. (Berl.)40 (1977), 123–128.

    Google Scholar 

  14. Dorfman, A., Ho, P.-L., Synthesis of acid mucopolysaccharides by glial tumor cells in tissue culture. Proc. Natl. Acad. Sci. U.S.A.66 (1970), 495–499.

    PubMed  Google Scholar 

  15. Drew, S. I., Terasaki, P. I., Billing, R. J., Bergh, O. J., Minowada, J. Klein, E., Group-specific human granulocyte antigens on a chronic myelogenous leukemia cell line with a Philadelphia chromosome marker. Blood49 (1977), 715–718.

    PubMed  Google Scholar 

  16. Fraser, J. R. E., Clarris, B. J., On the reaction of human synovial cells exposed to homologous leukocytes in vitro. Clin. Exp. Immunol.6 (1970), 211–225.

    PubMed  Google Scholar 

  17. Friedman, S. M., Neyhard, N., Chess, L., Cell-mediated lympholysis of trinitrophenyl-derivatized autologous human cells: in vitro triggering by nonspecific signals. J. Immunol.120 (1978), 630–637.

    PubMed  Google Scholar 

  18. Gately, M. K., Glaser, M., Dick, S. J., Mettetal, R. W., Jr., Kornblith, P. L., In vitro studies on the cell-mediated immune response to human brain tumors. I. Requirement for third-party stimulator lymphocytes in the induction of cytolytic T lymphocyte responses to allogeneic cultured gliomas. J. Natl. Cancer Inst. In press.

  19. Gately, M. K., Martz, E., Comparative studies on the mechanisms of nonspecific Con A-dependent cytolysis and specific T cell-mediated cytolysis. J. Immunol.119 (1977), 1711–1722.

    PubMed  Google Scholar 

  20. Glimelius, B., Norling, B., Westermark, B., Wasteson, A., Composition and distribution of glycosaminoglycans in cultures of human normal and malignant glial cells. Biochem. J.172 (1978), 443–456.

    PubMed  Google Scholar 

  21. Herberman, R. B., Cell-mediated immunity to tumor cells. Adv. Cancer Res.19 (1974), 207–263.

    PubMed  Google Scholar 

  22. Kano, I., Friedman, H., Immunosuppression and the role of suppressive factors in cancer. Adv. Cancer Res.25 (1977), 271–321.

    PubMed  Google Scholar 

  23. Kern, D. E., Gillis, S., Okada, M., Henney, C. S., The role of interleukin-2 IL-2) in the differentiation of cytotoxic T cells: The effect of monoclonal anti-IL-2 antibody and absorption with IL-2 dependent T cell lines. J. Immunol.127 (1981), 1323–1328.

    PubMed  Google Scholar 

  24. Kernohan, J. W., Sayre, G. P., Tumors of the central nervous system. Washington D.C.: Armed Forces Institute of Pathology, 1952.

    Google Scholar 

  25. Kumar, S., Taylor, G., Steward, J. K., Waghe, M. A., Morris-Jones, P., Cell-mediated immunity and blocking factors in patients with tumours of the central nervous system. Int. J. Cancer12 (1973), 194–205.

    PubMed  Google Scholar 

  26. Lafferty, K. J., Misko, I. S., Cooley, M. A., Allogeneic stimulation modulates the in vitro response of T cells to transplantation antigen. Nature249 (1974), 275–276.

    PubMed  Google Scholar 

  27. Lee, S. K., Oliver, R. T. D., Autologous leukemia-specific T-cell-mediated lymphocytotoxicity in patients with acute myelogenous leukemia. J. Exp. Med.147 (1978), 912–922.

    PubMed  Google Scholar 

  28. Levy, N. L., Specificity of lymphocyte-mediated cytotoxicity in patients with primary intracranial tumors. J. Immunol.121 (1978), 903–915.

    PubMed  Google Scholar 

  29. Masucci, M. G., Klein, E., Argov, S., Disappearance of the NK effect after explantation of lymphocytes and generation of similar nonspecific cytotoxicity correlated to the level of blastogenesis in activated cultures. J. Immunol.124 (1980), 2458–2463.

    PubMed  Google Scholar 

  30. McBride, W. H., Bard, J. B. L., Hyaluronidase-sensitive halos around adherent cells. Their role in blocking lymphocyte-mediated cytolysis. J. Exp. Med.149 (1979), 507–515.

    PubMed  Google Scholar 

  31. Ohya, T., Kaneko, T., Novel hyaluronidase from streptomyces. Biochem. Biophys. Acta198 (1970), 607–609.

    PubMed  Google Scholar 

  32. Okada, M., Klimpel, G. R., Kuppers, R. C., Henney, C. S., The differentiation of cytotoxic T cells in vitro. I. Amplifying factor(s) in the primary response is Lyt 1 + cell dependent. J. Immunol.122 (1979), 2527–2533.

    PubMed  Google Scholar 

  33. Perper, R. J., Zee, T. W., Mickelson, M. M., Purification of lymphocytes and platelets by gradient centrifugation. J. Lab. Clin. Med.72 (1968), 842–848.

    PubMed  Google Scholar 

  34. Pfrendschuh, M., Shiku, H., Takahashi, T., Ueda, R., Ransohoff, J., Oettgen, H. F., Old, L. J., Serological analysis of cell surface antigens of malignant human brain tumors. Proc. Nad. Acad. Sci. U.S.A.75 (1978), 5122–5126.

    Google Scholar 

  35. Pontén, J., Neoplastic human glial cells in culture. In: Human tumor cells in vitro (Fogh, J., ed.), pp. 175–206. New York: Plenum Press. 1975.

    Google Scholar 

  36. Röllinghoff, M., Wagner, H., Effect of M-locus dependent T-cell proliferation upon the induction of anti H-2 cytotoxic T effector cells. J. Immunogen. 2 (1975), 301–308.

    Google Scholar 

  37. Seeley, J. K., Masucci, G., Poros, A., Klein, E., Golub, S. H., Studies on cytotoxicity generated in human mixed lymphocyte cultures. II. Anti-K 562 effectors are distinct from allospecific CTL and can be generated from NK-depleted T cells. J. Immunol.123 (1979), 1303–1311.

    PubMed  Google Scholar 

  38. Sheikh, K. M. A., Apuzzo, M. L. J., Weiss, M. H., Specific cellular immune responses in patients with malignant gliomas. Cancer Res.39 (1979), 1733–1738.

    PubMed  Google Scholar 

  39. Sondel, P. M., O'Brien, C., Porter, L., Schlossmann, S. F., Chess, L., Cell-mediated destruction of human leukemic cells by MHC identical lymphocytes: A requirement for a proliferative triggerin vitro. J. Immunol.117 (1976), 2197–2203.

    PubMed  Google Scholar 

  40. Sopori, M. L., Alter, B. J., Bach, F. H., Cell-free factor substitute for “signal 2” in generating cytotoxic reactions. Eur. J. Immunol.7 (1977), 823–825.

    PubMed  Google Scholar 

  41. Trachtenberg, M. C., Kornblith, P. L., Hauptli, J., Biophysical properties of cultured human glial cells. Brain Res.38 (1972), 279–298.

    PubMed  Google Scholar 

  42. Trouillas, P., Immunologie et immunothérapie des tumeurs cérébrales. Etat Actuel Rev. Neurol.128 (1973), 23–38.

    Google Scholar 

  43. Walker, M. D., Alexander, E., Jr., Hunt, W. E., MacCarty, C. S., Mahaley, M. S., Jr., Mealey, J., Jr., Norrell, H. A., Owens, G., Ransohoff, J., Nilson, C. B., Gehan, E. A., Strike, T. A., Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J. Neurosurg.49 (1978), 333–343.

    PubMed  Google Scholar 

  44. Weinberger, O., Herrmann, S., Mescher, M. F., Benacerraf, B., Burakoff, S. J., Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: Evidence for antigen processing. Proc. Natl. Acad. Sci. U.S.A.78 (1981), 1796–1799.

    PubMed  Google Scholar 

  45. Weinstein, R. S., Kornblith, P. L., Ultrastructure of a cloned astrocytoma in tissue culture. Cancer27 (1971), 1174–1181.

    Google Scholar 

  46. Whisler, R. L., Yates, A. J., Regulation of lymphocyte responses by human gangliosides. I. Characteristics of inhibitory effects and the induction of impaired activation. J. Immunol.125 (1980), 2106–2111.

    PubMed  Google Scholar 

  47. Woosley, R. E., Mahaley, M. S., Jr., Mahaley, J. L., Miller, G. M., Brooks, W. H., Immunobiology of primary intracranial tumors. Part 3: Micro-cytotoxicity assays of specific immune responses of brain tumor patients. J. Neurosurg.47 (1977), 871–885.

    PubMed  Google Scholar 

  48. Young, H. F., Sakalas, R., Kaplan, A. M., Inhibition of cell-mediated immunity in patients with brain tumors. Surg. Neurol.5 (1976), 19–23.

    PubMed  Google Scholar 

  49. Zarling, J. M., Kung, P. C., Monoclonal antibodies which distinguish between human NK cells and cytotoxic T lymphocytes. Nature288 (1980), 394–396.

    PubMed  Google Scholar 

  50. Zarling, J. M., Raich, P. C., McKeough, M., Bach, F. H., Generation of cytotoxic lymphocytes in vitro against autologous human leukaemia cells. Nature262 (1976), 691–693.

    PubMed  Google Scholar 

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Author notes

  1. M. K. Gately

    Present address: Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

Authors and Affiliations

  1. Surgical Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

    M. Glaser, R. M. McCarron, S. J. Dick, M. D. Dick, R. W. Mettetal Jr. & P. L. Kornblith

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  1. M. K. Gately
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  2. M. Glaser
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  4. S. J. Dick
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  6. R. W. Mettetal Jr.
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  7. P. L. Kornblith
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Gately, M.K., Glaser, M., McCarron, R.M. et al. Mechanisms by which human gliomas may escape cellular immune attack. Acta neurochir 64, 175–197 (1982). https://doi.org/10.1007/BF01406052

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