Skip to main content
Log in

The Fas Counterattack: A Molecular Mechanism of Tumor Immune Privilege

  • Minireviews
  • Published:
Molecular Medicine Aims and scope Submit manuscript

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

References

  1. Nagata S, Golstein P. (1995) The Fas death factor. Science 267: 1449–1456.

    Article  CAS  PubMed  Google Scholar 

  2. Yonehara S, Nishimura Y, Kishil S, et al. (1994) Involvement of apoptosis antigen Fas in clonal deletion of human thymocytes. Int. Immunol. 6: 1849–1856.

    Article  CAS  PubMed  Google Scholar 

  3. Alderson MR, Tough TW, Davis-Smith T, et al. (1995) Fas ligand mediates activation-induced cell death in human T lymphocytes. J. Exp. Med. 181: 71–77.

    Article  CAS  PubMed  Google Scholar 

  4. Daniel PT, Krammer PH. (1994) Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells. J. Immunol. 152: 5624–5632.

    PubMed  CAS  Google Scholar 

  5. Ju ST, Cui H, Panka DJ, Ettinger R, Marshak-Rothstein A. (1994) Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and CD8+ cytotoxic T cells. Froc. Natl. Acad. Sci. U.S.A. 91: 4185–4189.

    Article  CAS  Google Scholar 

  6. Berke G. (1995) The CTL’s kiss of death. Cell 81: 9–12.

    Article  CAS  PubMed  Google Scholar 

  7. Stalder T, Hahn S, Erb P. (1994) Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity. J. Immunol. 152: 1127–1133.

    PubMed  CAS  Google Scholar 

  8. Montel AH, Bochan MR, Hobbs JA, Lynch DA, Brahmi Z. (1995) Fas involvement in cytotoxicity mediated by human NK cells. Cell. Immunol. 166: 236–246.

    Article  CAS  PubMed  Google Scholar 

  9. Trauth BC, Klas C, Peters AMJ, et al. (1989) Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245: 301–305.

    Article  CAS  PubMed  Google Scholar 

  10. Coney LR, Daniel PT, Sanborn D, et al. (1994) Apoptotic cell death induced by a mouse-human anti-APO-1 chimeric antibody leads to tumor regression. Int. J. Cancer 58: 562–567.

    Article  CAS  PubMed  Google Scholar 

  11. Lucking-Famira KM, Daniel PT, Möller P, Krammer PH, Debatin KM. (1994) APO-1 (CD95) mediated apoptosis in human T-ALL engrafted in SCID mice. Leukemia 8: 1825–1833.

    PubMed  CAS  Google Scholar 

  12. Suda T, Okazaki T, Naito Y, et al. (1995) Expression of the Fas ligand in cells of T cell lineage. J. Immunol. 154: 3806–3813.

    PubMed  CAS  Google Scholar 

  13. Hahne M, Renno T, Schroeter M, et al. (1996) Activated B cells express functional Fas ligand. Eur. J. Immunol. 26: 721–724.

    Article  CAS  PubMed  Google Scholar 

  14. Liles WC, Kiener PA, Ledbetter JA, Aruffo A, Klebanoff SJ. (1996) Differential expression of Fas (CD95) and Fas ligand on normal human phagocytes: Implications for the regulation of apoptosis in neutrophils. J. Exp. Med. 184: 429–440.

    Article  CAS  PubMed  Google Scholar 

  15. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. (1995) Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270: 1189–1192.

    Article  CAS  PubMed  Google Scholar 

  16. Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC. (1995) A role for CD95 ligand in preventing graft rejection. Nature 377: 630–632.

    Article  CAS  PubMed  Google Scholar 

  17. O’Connell J, O’Sullivan GC, Collins JK, Shanahan F. (1996) The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J. Exp. Med. 184: 1075–1082.

    Article  PubMed  Google Scholar 

  18. Hahne M, Rimoldi D, Schroter M, et al. (1996) Melanoma cell expression of Fas(Apo-l/CD95) ligand: Implications for tumor immune escape. Science 274: 1363–1366.

    Article  CAS  PubMed  Google Scholar 

  19. Strand S, Hofmann WJ, Hug H, et al. (1996) Lymphocyte apoptosis induced by CD9 5 (Apo-l/Fas) ligand-expressing tumor cells—a mechanism of immune evasion? Nat. Med. 2: 1361–1366.

    Article  CAS  PubMed  Google Scholar 

  20. Robertson MJ, Manley TJ, Richert G, et al. (1995) Functional consequences of APO-1/ Fas (CD95) antigen expression by normal and neoplastic hematopoietic cells. Leuk. Lymphoma. 17: 51–61.

    Article  CAS  PubMed  Google Scholar 

  21. Kotani T, Aratake Y, Kondo S, Tamura K, Ohtaki S. (1994) Expression of functional Fas antigen on adult T-cell leukemia. Leuk. Res. 18: 305–310.

    Article  CAS  PubMed  Google Scholar 

  22. Massaia M, Borrione P, Attisano C, et al. (1995) Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients. Blood 85: 3679–3687.

    PubMed  CAS  Google Scholar 

  23. Westendorf JJ, Lammert JM, Jelinek DF. (1995) Expression and function of Fas (APO-1/CD95) in patient myeloma cells and myeloma cell lines. Blood 85: 3566–3576.

    PubMed  CAS  Google Scholar 

  24. Shima Y, Nishimoto N, Ogata A, Fujii Y, Yoshizaki K, Kishimoto T. (1995) Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood 85: 757–764.

    PubMed  CAS  Google Scholar 

  25. Hata H, Matsuzaki H, Takeya M, et al. (1995) Expression of Fas/Apo-1 (CD95) and apoptosis in tumor cells from patients with plasma cell disorders. Blood 86: 1939–1945.

    PubMed  CAS  Google Scholar 

  26. Mori S, Murakami-Mori K, Jewett A, Nakamura S, Bonavida B. (1996) Resistance of AID S-associated Kaposi’s sarcoma cells to Fas-mediated apoptosis. Cancer Res. 56: 1874–1879.

    PubMed  CAS  Google Scholar 

  27. Owen-Schaub LB, Radinsky R, Kruzel E, Berry K, Yonehara S. (1994) Anti-Fas on nonhematopoietic tumors: Levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res. 54: 1580–1586.

    PubMed  CAS  Google Scholar 

  28. Weiler M, Frei K, Groscurth P, Krammer PH, Yonekawa Y, Fontana A. (1994) Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J. Clin. Invest. 94: 954–964.

    Article  Google Scholar 

  29. Keane MM, Ettenberg SA, Lowrey GA, Russell EK, Lipkowitz S. (1996) Fas expression and function in normal and malignant breast cell lines. Cancer Res. 56: 4791–4798.

    PubMed  CAS  Google Scholar 

  30. Möller P, Koretz K, Leithauser F, et al. (1994) Expression of APO-1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium. Int. J. Cancer 57: 371–377.

    Article  PubMed  Google Scholar 

  31. Knipping E, Debatin K-M, Strieker K, Heilig B, Edar A, Krammer PH. (1995) Identification of soluble APO-1 in supernatants of human B- and T-cell lines and increased serum levels in B- and T-cell leukemias. Blood 85: 1562–1569.

    PubMed  CAS  Google Scholar 

  32. Owen-Schaub LB, Angelo LS, Radinsky R, Ware CF, Gesner TG, Bartos DP. (1995) Soluble Fas/APO-1 in tumor cells: A potential regulator of apoptosis? Cancer Lett. 94: 1–8.

    Article  CAS  PubMed  Google Scholar 

  33. Tachibana O, Nakazawa H, Lampe J, Watanabe K, Kleihues P, Ohgaki H. (1995) Expression of Fas/APO-1 during the progression of astrocytomas. Cancer Res. 55: 5528–5530.

    PubMed  CAS  Google Scholar 

  34. Natoli G, Ianni A, Costanzo A, et al. (1995) Resistance to Fas-mediated apoptosis in human hepatoma cells. Oncogene 11: 1157–1164.

    PubMed  CAS  Google Scholar 

  35. Cascino I, Papoff G, De Maria R, Testi R, Ruberti G. (1996) Fas/Apo-1 (CD95) receptor lacking the intracytoplasmic signaling domain protects tumor cells from Fas-mediated apoptosis. J. Immunol. 156: 13–17.

    PubMed  CAS  Google Scholar 

  36. Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM. (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81: 505–512.

    Article  CAS  PubMed  Google Scholar 

  37. Stanger BZ, Leder P, Lee TH, Kim E, Seed B. (1995) RIP: A novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81: 513–523.

    Article  CAS  PubMed  Google Scholar 

  38. Chu K, Niu X, Williams LT. (1995) A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc. Natl. Acad. Sci. U.S.A. 92: 11894–11898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Muzio M, Chinnaiyan AM, Kischkel FC, et al. (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85: 817–827.

    Article  CAS  PubMed  Google Scholar 

  40. Sato T, Irie S, Kitada S, Reed JC. (1995) FAP-1: A protein tyrosine phosphatase that associates with Fas. Science 268: 411–415.

    Article  CAS  PubMed  Google Scholar 

  41. Okura T, Gong L, Kamitani T, et al. (1996) Protection against Fas/Apo-1 and tumor necrosis factor-mediated cell death by a novel protein, sentrin. J. Immunol 157: 4277–4281.

    PubMed  CAS  Google Scholar 

  42. Enari M, Talanian RV, Wong WW, Nagata S. (1996) Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature 380: 723–726.

    Article  CAS  PubMed  Google Scholar 

  43. Los M, van de Craen M, Penning LC, et al. (1995) Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature 375: 81–83.

    Article  CAS  PubMed  Google Scholar 

  44. Srinivasula SM, Ahmad M, Fernandes-Al-nemri T, Litwack G, Alnemri ES. (1996) Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc. Natl. Acad. Sci. U.S.A. 93: 14486–14491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tamura T, Ueda S, Yoshida M, Matsuzaki M, Mohri H, Okubo T. (1996) IFN-gamma induces ICE gene expression and enhances cellular susceptibility to apoptosis in the U937 leukemia cell line. Biochem. Biophys. Res. Commun. 229: 21–26.

    Article  CAS  PubMed  Google Scholar 

  46. Su X, Zhou T, Wang Z, Yang P, Jope RS, Mountz JD. (1995) Defective expression of hematopoietic cell protein tyrosine phosphatase (HCP) in lymphoid cells blocks Fas-mediated apoptosis. Immunity 2: 353–362.

    Article  CAS  PubMed  Google Scholar 

  47. Itoh N, Tsujimoto Y, Nagata S. (1993) Effect of bcl-2 on Fas antigen-mediated cell death. J. Immunol. 151: 621–627.

    PubMed  CAS  Google Scholar 

  48. Weller M, Malipiero U, Aguzzi A, Reed JC, Fontana A. (1995) Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J. Clin. Invest. 95: 2633–2643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jaattela M, Benedict M, Tewari M, Shayman JA, Dixit VM. (1995) Bcl-x and bcl-2 inhibit TNF and Fas-induced apoptosis and activation of phospholipase A2 in breast carcinoma cells. Oncogene 10: 2297–2305.

    PubMed  CAS  Google Scholar 

  50. Bargou RC, Daniel PT, Mapara MY, et al. (1995) Expression of the bcl-2 gene family in normal and malignant breast tissue: Low bax-alpha expression in tumor cells correlates with resistance towards apoptosis. Int. J. Cancer 60: 854–859.

    Article  CAS  PubMed  Google Scholar 

  51. Bargou RC, Wagener C, Bommert K, et al. (1996) Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice. J. Clin. Invest. 97: 2651–2659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tamura T, Aoyama N, Saya H, et al. (1995) Induction of Fas-mediated apoptosis in p53-transfected human colon carcinoma cells. Oncogene 11: 1939–1946.

    PubMed  CAS  Google Scholar 

  53. Owen-Schaub LB, Zhang W, Cusack JC, et al. (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol. Cell Biol 15: 3032–3040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. McGahon AJ, Nishioka WK, Martin SJ, Mahboubi A, Cotter TG, Green DR. (1995) Regulation of the Fas apoptotic cell death pathway by Abl. J. Biol. Chem. 270: 22625–22631.

    Article  CAS  PubMed  Google Scholar 

  55. Korbutt GS, Elliott JF, Rajotte RV. (1997) Cotransplantation of allogeneic islets with allogeneic testicular cell aggregates allows long-term graft survival without systemic immunosuppression. Diabetes 46: 317–322.

    Article  CAS  PubMed  Google Scholar 

  56. Lau HT, Yu M, Fontana A, Stoeckert CJ, Jr. (1996) Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 270: 109–112.

    Article  Google Scholar 

  57. Stuart PM, Griffith TS, Usui N, Pepose J, Yu X, Ferguson TA. (1997) CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival. J. Clin. Invest. 99: 396–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Tanaka M, Suda T, Haze K, et al. (1996) Fas ligand in human serum. Nat. Med. 2: 317–322.

    Article  CAS  PubMed  Google Scholar 

  59. Zornig M, Grzeschiczek A, Kowalski MB, Hartmann KU, Moroy T. (1995) Loss of Fas/Apo-1 receptor accelerates lymphomagenesis in E mu L-Myc transgenic mice but not in animals infected with MoMuLV. Oncogene 10: 2397–2401.

    PubMed  CAS  Google Scholar 

  60. Peng SL, Robert ME, Hayday AC, Craft J. (1996) A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice. J. Exp. Med. 184: 1149–1154.

    Article  CAS  PubMed  Google Scholar 

  61. van den Broek ME, Kagi D, Ossendorp F, et al. (1996) Decreased tumor surveillance in perforin-deficient mice. J. Exp. Med. 184: 1781–1790.

    Article  PubMed  Google Scholar 

  62. Irmler M, Hertig S, MacDonald HR, et al. (1995) Granzyme A is an interleukin 1 beta-converting enzyme. J. Exp. Med. 181: 1917–1922.

    Article  CAS  PubMed  Google Scholar 

  63. Quan LT, Caputo A, Bleackley RC, Pickup DJ, Salvesen GS. (1995) Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A. J. Biol. Chem. 270: 10377–10379.

    Article  CAS  PubMed  Google Scholar 

  64. Kondo S, Barna BP, Morimura T, et al. (1995) Interleukin-1β converting enzyme mediates cisplatin-induced apoptosis in malignant glioma cells. Cancer Res. 55: 6166–6171.

    PubMed  CAS  Google Scholar 

  65. Schroter M, Lowin B, Borner C, Tschopp J. (1995) Regulation of Fas(Apo-l/CD95)- and perforin-mediated lytic pathways of primary cytotoxic T lymphocytes by the protooncogene bcl-2. Eur. J. Immunol. 25: 3509–3513.

    Article  CAS  PubMed  Google Scholar 

  66. Minn AJ, Rudin CM, Boise LH, Thompson CB. (1995) Expression of bcl-xL can confer a multi-drug resistance phenotype. Blood 86: 1903–1910.

    PubMed  CAS  Google Scholar 

  67. Schott AF, Apel IJ, Nunez G, Clarke MF. (1995) Bcl-xL proteas cancer cells from p53-mediated apoptosis. Oncogene 11: 1389–1394.

    PubMed  CAS  Google Scholar 

  68. Friesen C, Herr I, Krammer PH, Debatin K-M. (1996) Involvement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat. Med. 2: 574–577.

    Article  CAS  PubMed  Google Scholar 

  69. Müller M, Strand S, Hug H, et al. (1997) Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J. Clin. Invest. 99: 403–413.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Rayner AA, Grimm EA, Lotze MT. (1985) Lymphokine-activated killer (LAK) cells: Analysis of factors relevant to the immunotherapy of human cancer. Cancer 55: 1327–1333.

    Article  CAS  PubMed  Google Scholar 

  71. Weiler M, Malipiero U, Rensing-Ehl A, Barr PJ, Fontana A. (1995) Fas/APO-1 gene transfer for human malignant glioma. Cancer Res. 55: 2936–2944.

    Google Scholar 

  72. Browning JL, Miatkowski K, Sizing I, et al. (1996) Signaling through the lymphotoxin-beta receptor induces the death of some adenocarcinoma tumor lines. J. Exp. Med. 183: 867–878.

    Article  CAS  PubMed  Google Scholar 

  73. Abreu-Martin MT, Vidrich A, Lynch DH, Targan SR. (1995) Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen. J. Immunol 155: 4147–4154.

    PubMed  CAS  Google Scholar 

  74. Ogasawara J, Watanabe-Fukunaga R, Adachi M, et al. (1993) Lethal effect of the anti-Fas antibody in mice. Nature 364: 806–809.

    Article  CAS  PubMed  Google Scholar 

  75. Rodriguez I, Matsuura K, Ody C, Nagata S, Vassalli P. (1996) Systemic injection of a tripeptide inhibits the intracellular activation of CPP32-like proteases in vivo and fully protects mice against Fas-mediated fulminant liver destruction and death. J. Exp. Med. 184: 2067–2072.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fergus Shanahan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Connell, J., Bennett, M.W., O’Sullivan, G.C. et al. The Fas Counterattack: A Molecular Mechanism of Tumor Immune Privilege. Mol Med 3, 294–300 (1997). https://doi.org/10.1007/BF03401808

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03401808

Keywords

Navigation