Journal of Neuro-Oncology

, Volume 40, Issue 3, pp 233–235 | Cite as

Soluble CD95 (Fas/APO-1) in Malignant Glioma: (No) Implications for CD95-based Immunotherapy?

  • Johannes R. Streffer
  • Monika Schuster
  • Frauke Zipp
  • Michael Weller


CD95 targeting is a novel approach of immunotherapy for malignant glioma that might be antagonized by the release of soluble CD95 by the tumor cells. An alternatively spliced CD95 mRNA that encodes a secreted CD95 variant has been detected in glioma cell lines in vitro and in human tumors in vivo. Here, we report that the levels of soluble CD95 in the serum of malignant glioma patients do not differ from those of lumbar disk disease patients. Soluble CD95 was detected in the CSF in 2 of 20 malignant glioma patients by ELISA. Bioassay studies indicate that these low levels of soluble CD95 in the CSF of some patients with malignant glioma cells are unlikely to interfere with CD95-based immunotherapy of malignant gliomas in vivo.

CD95 glioma apoptosis CSF brain 


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  1. 1.
    Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kasugai T, Kitamura Y, Itoh N, Suda T, Nagata S: Lethal effect of the anti-Fas antibody in mice. Nature 364: 806–809, 1993Google Scholar
  2. 2.
    Weller M, Kleihues P, Dichgans J, Ohgaki H: CD95 ligand: lethal weapon against malignant glioma? Brain Pathol 8: 285–293, 1998Google Scholar
  3. 3.
    Becher B, D'Souza SD, Troutt AB, Antel JP: Fas expression on human fetal astrocytes without susceptibility to Fas-mediated cytotoxicity. Neuroscience 84: 627–634, 1998Google Scholar
  4. 4.
    Leithäuser F, Dhein J, Mechtersheimer G, Koretz K, Brüderlein S, Henne C, Schmidt A, Debatin KM, Krammer PH, Möller P: Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor superfamily, in normal and neoplastic cells. Lab Invest 69: 415–429, 1993Google Scholar
  5. 5.
    Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PI, Mountz JD: Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263: 1759–1762, 1994Google Scholar
  6. 6.
    Zipp F, Weller M, Calabresi PA, Frank JA, Bash CN, Dichgans J, McFarland HF, Martin R: Increased serum levels of soluble CD95 (APO-1/Fas) in relapsing remitting multiple sclerosis. Ann Neurol 43: 116–120, 1998Google Scholar
  7. 7.
    Zipp F, Ötzelberger K, Dichgans J, Martin R, Weller M: Serum CD95 of multiple sclerosis patients protects from CD95-mediated apoptosis. J Neuroimmunol 86:151–154, 1998Google Scholar
  8. 8.
    Owen-Schaub LB, Angelo LS, Radinsky R, Ware CF, Gesner TG, Bartos DP: Solublc Fas/APO-1 in tumor cells: a potential regulator of apoptosis? Cancer Lett 94: 1–8, 1995Google Scholar
  9. 9.
    Midis GP, Shen Y, Owen-Schaub LB: Elevated soluble Fas (sFas) levels in nonhematopoietic human malignancy. Cancer Res 56: 3870–3874, 1996Google Scholar
  10. 10.
    Weller M, Malipiero U, Rensing-Ehl A, Barr P, Fontana A: Fas/APO-1 gene transfer for human malignant glioma. Cancer Res 55: 2936–2944, 1995Google Scholar
  11. 11.
    Tachibana O, Nakazawa H, Lampe J, Watanabe K, Kleihues P, Ohgaki H: Expression of Fas/APO-1 during the progression of astrocytomas. Cancer Res 55: 5528–5530, 1995Google Scholar
  12. 12.
    Roth W, Fontana A, Trepel M, Dichgans J, Reed JC, Weller M. Immunochemotherapy of malignant glioma: synergistic activity of CD95 ligand and chemotherapeutics. Cancer Immunol Immunother 44: 55–63, 1997Google Scholar
  13. 13.
    Saas P, Walker PR, Hahne M, Quiquerez AL, Schnuriger V, Perrin G, French L, van Meir EG, de Tribolet N, Tschopp J, Dietrich PY. Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain? J Clin Invest 9: 1173–1178, 1997Google Scholar
  14. 14.
    Gratas C, Tohma Y, Van Meir EG, Klein M, Tenan M, Ishii N, Tachibana O, Kleihues P, Ohgaki H. Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Brain Pathol 7: 863–869, 1997Google Scholar
  15. 15.
    Weller M, Weinstock C, Will C, Wagenknecht B, Dichgans J, Lang F, Gulbins E. CD95-dependent T-cell killing by glioma cells expressing CD95 ligand: more on tumor escape, the CD95 counterattack, and the immune privilege of the brain. Cell Physiol Biochem 7: 282–288, 1997Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Johannes R. Streffer
    • 1
  • Monika Schuster
    • 1
  • Frauke Zipp
    • 1
  • Michael Weller
    • 1
  1. 1.Laboratory of Molecular Neuro-Oncology, Department of NeurologyUniversity of Tübingen, School of MedicineTübingenGermany

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