Skip to main content

Advertisement

SpringerLink
Log in

Tumor counterattack: fact or fiction?

  • Symposium Paper
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Cancer development relies on a variety of mechanisms that facilitate tumor growth despite the presence of a functioning immune system. Understanding these mechanisms may foster novel therapeutic approaches for oncology and organ transplantation. By expression of the apoptosis-inducing protein CD95L (FasL, APO-1L, CD178), tumors may eliminate tumor-infiltrating lymphocytes and suppress anti-tumor immune responses, a phenomenon called “tumor counterattack”. On the one hand, preliminary evidence of tumor counterattack in human tumors exists, and CD95L expression can prevent T-cell responses in vitro. On the other hand, CD95L-expressing tumors are rapidly rejected and induce inflammation in mice. Here, we summarize and discuss the consequences of CD95L expression of tumor cells and its contribution to immune escape.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Alderson MR, Tough TW, Braddy S, Davis-Smith T, Roux E, Schooley K, Miller RE, Lynch DH (1994) Regulation of apoptosis and T cell activation by Fas-specific mAb. Int Immunol 6:1799–1806

    CAS  PubMed  Google Scholar 

  2. Allison J, Georgiou HM, Strasser A, Vaux DL (1997) Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc Natl Acad Sci U S A 94:3943–3947

    Article  CAS  PubMed  Google Scholar 

  3. Aoki K, Kurooka M, Chen JJ, Petryniak J, Nabel EG, Nabel GJ (2001) Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity. Nat Immunol 2:333–337

    Article  CAS  PubMed  Google Scholar 

  4. Arai H, Chan SY, Bishop DK, Nabel GJ (1997) Inhibition of the alloantibody response by CD95 ligand. Nat Med 3:843–848

    Article  CAS  PubMed  Google Scholar 

  5. Arai H, Gordon D, Nabel EG, Nabel GJ (1997) Gene transfer of Fas ligand induces tumor regression in vivo. Proc Natl Acad Sci U S A 94:13862–13867

    Article  CAS  PubMed  Google Scholar 

  6. Askenasy N, Yolcu ES, Wang Z, Shirwan H (2003) Display of Fas ligand protein on cardiac vasculature as a novel means of regulating allograft rejection. Circulation 107:1525–1531

    Article  CAS  PubMed  Google Scholar 

  7. Barnhart BC, Legembre P, Pietras E, Bubici C, Franzoso G, Peter ME (2004) CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells. Embo J 23:3175–3185

    Article  CAS  PubMed  Google Scholar 

  8. Behrens CK, Igney FH,Arnold B, Moller P, Krammer PH (2001) CD95 ligand-expressing tumors are rejected in anti-tumor TCR transgenic perforin knockout mice. J Immunol 166:3240–3247

    CAS  PubMed  Google Scholar 

  9. 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 

  10. Bennett MW, O’Connell J, O’Sullivan GC, Roche D, Brady C, Kelly J, Collins JK, Shanahan F (1999) Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer. Gut 44:156–162

    CAS  PubMed  Google Scholar 

  11. Bennett MW, O’Connell J, O’Sullivan GC, Brady C, Roche D, Collins JK, Shanahan F (1998) The Fas counterattack in vivo: apoptotic depletion of tumor- infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol 160:5669–5675

    CAS  PubMed  Google Scholar 

  12. Bossi G, Griffiths GM (1999) Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells. Nat Med 5:90–96

    Article  CAS  PubMed  Google Scholar 

  13. Buonocore S, Van Meirvenne S, Demoor F, Paulart F, Thielemans K, Goldman M, Flamand V (2003) Dendritic cells overexpressing CD95 (Fas) ligand elicit vigorous allospecific T-cell responses in vivo. Blood 101:1469–1476

    Article  CAS  PubMed  Google Scholar 

  14. Chang MK, Binder CJ, Miller YI, Subbanagounder G, Silverman GJ, Berliner JA, Witztum JL (2004) Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med 200:1359–1370

    Article  CAS  PubMed  Google Scholar 

  15. Chen JJ, Sun Y, Nabel GJ (1998) Regulation of the proinflammatory effects of Fas ligand (CD95L). Science 282:1714–1717

    Article  CAS  PubMed  Google Scholar 

  16. Chen YL, Chen SH, Wang JY, Yang BC (2003) Fas ligand on tumor cells mediates inactivation of neutrophils. J Immunol 171:1183–1191

    CAS  PubMed  Google Scholar 

  17. Choi C, Park JY, Lee J, Lim JH, Shin EC, Ahn YS, Kim CH, Kim SJ, Kim JD, Choi IS, Choi IH (1999) Fas ligand and Fas are expressed constitutively in human astrocytes and the expression increases with IL-1, IL-6, TNF-alpha, or IFN-gamma. J Immunol 162:1889–1895

    CAS  PubMed  Google Scholar 

  18. Desbarats J, Birge RB, Mimouni-Rongy M, Weinstein DE, Palerme JS, Newell MK (2003) Fas engagement induces neurite growth through ERK activation and p35 upregulation. Nat Cell Biol 5:118–125

    Article  CAS  PubMed  Google Scholar 

  19. Deveraux QL, Reed JC (1999) IAP family proteins–suppressors of apoptosis. Genes Dev 13:239–252

    CAS  PubMed  Google Scholar 

  20. Dhein J, Walczak H, Bäumler C, Debatin KM, Krammer PH (1995) Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 373:438–441

    Article  CAS  PubMed  Google Scholar 

  21. Drozdzik M, Qian C, Lasarte JJ, Bilbao R, Prieto J (1998) Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL). Gene Ther 5:1622–1630

    Article  CAS  PubMed  Google Scholar 

  22. Dulat HJ, von Grumbkow C, Baars W, Schroder N, Wonigeit K, Schwinzer R (2001) Down-regulation of human alloimmune responses by genetically engineered expression of CD95 ligand on stimulatory and target cells. Eur J Immunol 31:2217–2226

    Article  CAS  PubMed  Google Scholar 

  23. Eichhorst ST, Muller M, Li-Weber M, Schulze-Bergkamen H, Angel P, Krammer PH (2000) A novel AP-1 element in the CD95 ligand promoter is required for induction of apoptosis in hepatocellular carcinoma cells upon treatment with anticancer drugs. Mol Cell Biol 20:7826–7837

    Article  CAS  PubMed  Google Scholar 

  24. Fadok VA, Bratton DL, Henson PM (2001) Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences. J Clin Invest 108:957–962

    Article  CAS  PubMed  Google Scholar 

  25. French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, Muller C, Tschopp J (1996) Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol 133:335–343

    Article  CAS  PubMed  Google Scholar 

  26. Friesen C, Fulda S, Debatin KM (1999) Induction of CD95 ligand and apoptosis by doxorubicin is modulated by the redox state in chemosensitive- and drug-resistant tumor cells. Cell Death Differ 6:471–480

    Article  CAS  PubMed  Google Scholar 

  27. Friesen C, Herr I, Krammer PH, Debatin KM (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 

  28. Fulda S, Scaffidi C, Pietsch T, Krammer PH, Peter ME, Debatin KM (1998) Activation of the CD95 (APO-1/Fas) pathway in drug- and gamma- irradiation-induced apoptosis of brain tumor cells. Cell Death Differ 5:884–893

    Article  CAS  PubMed  Google Scholar 

  29. Gao Y, Herndon JM, Zhang H, Griffith TS, Ferguson TA (1998) Antiinflammatory effects of CD95 ligand (FasL)-induced apoptosis. J Exp Med 188:887–896

    Article  CAS  PubMed  Google Scholar 

  30. Gratas C, Tohma Y, Van Meir EG, Klein M, Tenan M, Ishii N, Tachibana O, Kleihues P, Ohgaki H (1997) Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Brain Pathol 7:863–869

    CAS  PubMed  Google Scholar 

  31. 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

    CAS  PubMed  Google Scholar 

  32. Griffith TS, Yu X, Herndon JM, Green DR, Ferguson TA (1996) CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance. Immunity 5:7–16

    Article  CAS  PubMed  Google Scholar 

  33. Gutierrez-Steil C, Wrone-Smith T, Sun X, Krueger JG, Coven T, Nickoloff BJ (1998) Sunlight-induced basal cell carcinoma tumor cells and ultraviolet-B- irradiated psoriatic plaques express Fas ligand (CD95L). J Clin Invest 101:33–39

    CAS  PubMed  Google Scholar 

  34. Hahne M, Rimoldi D, Schroter M, Romero P, Schreier M, French LE, Schneider P, Bornand T, Fontana A, Lienard D, Cerottini J, Tschopp J (1996) Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science 274:1363–1366

    CAS  PubMed  Google Scholar 

  35. Hohlbaum AM, Gregory MS, Ju ST, Marshak-Rothstein A. (2001) Fas ligand engagement of resident peritoneal macrophages in vivo induces apoptosis and the production of neutrophil chemotactic factors. J Immunol 167:6217–6224

    CAS  PubMed  Google Scholar 

  36. Hohlbaum AM, Moe S, Marshak-Rothstein A. (2000) Opposing effects of transmembrane and soluble Fas ligand expression on inflammation and tumor cell survival. J Exp Med 191:1209–1220

    Article  CAS  PubMed  Google Scholar 

  37. Igney FH, Behrens CK, Krammer PH (2000) Tumor counterattack–concept and reality. Eur J Immunol 30:725–731

    Article  CAS  PubMed  Google Scholar 

  38. Igney FH, Behrens CK, Krammer PH (2003) The influence of CD95L expression on tumor rejection in mice. Eur J Immunol 33:2811–2821

    Article  CAS  PubMed  Google Scholar 

  39. Igney FH, Behrens CK, Krammer PH (2005) CD95L mediates tumor counterattack in vitro but induces neutrophil-independent tumor rejection in vivo. Int J Cancer 113:78–87

    Article  CAS  PubMed  Google Scholar 

  40. Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2:277–88

    Article  CAS  PubMed  Google Scholar 

  41. Igney FH, Krammer PH (2002) Immune escape of tumors: apoptosis resistance and tumor counterattack. J Leukoc Biol 71:907–20

    CAS  PubMed  Google Scholar 

  42. Judge TA, Desai NM, Yang Z, Rostami S, Alonso L, Zhang H, Chen Y, Markman JF, DeMateo RP, Barker CF, Naji A, Turka LA (1998) Utility of adenoviral-mediated Fas ligand gene transfer to modulate islet allograft survival. Transplantation 66:426–434

    Article  CAS  PubMed  Google Scholar 

  43. Kang SM, Braat D, Schneider DB, O’Rourke RW, Lin Z, Ascher NL, Dichek DA, Baekkeskov S, Stock PG (2000) A non-cleavable mutant of Fas ligand does not prevent neutrophilic destruction of islet transplants. Transplantation 69:1813–1817

    Article  CAS  PubMed  Google Scholar 

  44. Kang SM, Hoffmann A, Le D, Springer ML, Stock PG, Blau HM (1997) Immune response and myoblasts that express Fas ligand. Science 278:1322–1324

    Article  CAS  PubMed  Google Scholar 

  45. Kang SM, Schneider DB, Lin Z, Hanahan D, Dichek DA, Stock PG, Baekkeskov S (1997) Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med 3:738–743

    Article  CAS  PubMed  Google Scholar 

  46. Khar A, Varalakshmi C, Pardhasaradhi BV, Mubarak Ali A, Kumari AL (1998) Depletion of the natural killer cell population in the peritoneum by AK- 5 tumor cells overexpressing fas-ligand: a mechanism of immune evasion. Cell Immunol 189:85–91

    Article  CAS  PubMed  Google Scholar 

  47. Klas C, Debatin KM, Jonker RR, Krammer PH (1993) Activation interferes with the APO-1 pathway in mature human T cells. Int Immunol 5:625–630

    CAS  PubMed  Google Scholar 

  48. Krammer PH (1997) The tumor strikes back. Cell Death Differ 4:362–364

    Article  CAS  Google Scholar 

  49. Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795

    Article  CAS  PubMed  Google Scholar 

  50. Krueger A, Baumann S, Krammer PH, Kirchhoff S (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21:8247–8254

    Article  CAS  PubMed  Google Scholar 

  51. Krueger A, Fas SC, Baumann S, Krammer PH (2003) The role of CD95 in the regulation of peripheral T-cell apoptosis. Immunol Rev 193:58–69

    Article  CAS  PubMed  Google Scholar 

  52. Kume T, Oshima K, Yamashita Y, Shirakusa T, Kikuchi M (1999) Relationship between Fas-ligand expression on carcinoma cell and cytotoxic T-lymphocyte response in lymphoepithelioma-like cancer of the stomach. Int J Cancer 84:339–343

    Article  CAS  PubMed  Google Scholar 

  53. Kurooka M, Nuovo GJ, Caligiuri MA, Nabel GJ (2002) Cellular localization and function of Fas ligand (CD95L) in tumors. Cancer Res 62:1261–1265

    CAS  PubMed  Google Scholar 

  54. Kurts C, Heath WR, Kosaka H, Miller JF, Carbone FR (1998) The peripheral deletion of autoreactive CD8+ T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1). J Exp Med 188:415–420

    Article  CAS  PubMed  Google Scholar 

  55. Lau HT, Yu M, Fontana A, Stoeckert CJ Jr (1996) Prevention of islet allograft rejection with engineered myoblasts expressing FasL in mice. Science 273:109–112

    CAS  PubMed  Google Scholar 

  56. Li JH, Rosen D, Sondel P, Berke G (2002) Immune privilege and FasL: two ways to inactivate effector cytotoxic T lymphocytes by FasL-expressing cells. Immunology 105:267–277

    Article  CAS  PubMed  Google Scholar 

  57. Li XK, Okuyama T, Tamura A, Enosawa S, Kaneda Y, Takahara S, Funashima N, Yamada M, Amemiya H, Suzuki S (1998) Prolonged survival of rat liver allografts transfected with Fas ligand- expressing plasmid. Transplantation 66:1416–1423

    Article  CAS  PubMed  Google Scholar 

  58. Li-Weber M, Krammer PH (2003) Function and regulation of the CD95 (APO-1/Fas) ligand in the immune system. Semin Immunol 15:145–157

    Article  CAS  PubMed  Google Scholar 

  59. Lynch DH, Ramsdell F, Alderson MR (1995) Fas and FasL in the homeostatic regulation of immune responses. Immunol Today 16:569–745

    Article  CAS  PubMed  Google Scholar 

  60. Mariani SM, Krammer PH (1998) Differential regulation of TRAIL and CD95 ligand in transformed cells of the T and B lymphocyte lineage. Eur J Immunol 28:973–982

    Article  CAS  PubMed  Google Scholar 

  61. Mariani SM, Matiba B, Bäumler C, Krammer PH (1995) Regulation of cell surface APO-1/Fas (CD95) ligand expression by metalloproteases. Eur J Immunol 25:2303–2307

    CAS  PubMed  Google Scholar 

  62. Martinou JC, Green DR (2001) Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2:63–67

    Article  CAS  PubMed  Google Scholar 

  63. Matsue H, Matsue K, Walters M, Okumura K, Yagita H, Takashima A. (1999) Induction of antigen-specific immunosuppression by CD95L cDNA-transfected ‘killer’ dendritic cells. Nature Med 5:930–937

    Article  CAS  PubMed  Google Scholar 

  64. Min WP, Gorczynski R, Huang XY, Kushida M, Kim P, Obataki M, Lei J, Suri RM, Cattral MS (2000) Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival. J Immunol 164:161–167

    CAS  PubMed  Google Scholar 

  65. Miwa K, Asano M, Horai R, Iwakura Y, Nagata S, Suda T (1998) Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand. Nat Med 4:1287–1292

    Article  CAS  PubMed  Google Scholar 

  66. Muller M, Strand S, Hug H, Heinemann EM, Walczak H, Hofmann WJ, Stremmel W, Krammer PH, Galle PR (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

    CAS  PubMed  Google Scholar 

  67. Muller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, Friedman SL, Galle PR, Stremmel W, Oren M, Krammer PH (1998) p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J Exp Med 188:2033–2045

    Article  CAS  PubMed  Google Scholar 

  68. Nishimatsu H, Takeuchi T, Ueki T, Kajiwara T, Moriyama N, Ishida T, Li B, Kakizoe T, Kitamura T (1999) CD95 ligand expression enhances growth of murine renal cell carcinoma in vivo. Cancer Immunol Immunother 48:56–61

    Article  CAS  PubMed  Google Scholar 

  69. Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, Hemmi S, Hengartner H, Zinkernagel RM (2001) Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411:1058–1064

    CAS  PubMed  Google Scholar 

  70. O’Connell J, Houston A, Bennett MW, O’Sullivan GC, Shanahan F (2001) Immune privilege or inflammation? Insights into the Fas ligand enigma. Nat Med 7:271–274

    Article  CAS  PubMed  Google Scholar 

  71. Okamoto S, Takamizawa S, Bishop W, Wen J, Kimura K, Sandler A. (1999) Overexpression of Fas ligand does not confer immune privilege to a pancreatic beta tumor cell line (betaTC-3). J Surg Res 84:77–81

    Article  CAS  PubMed  Google Scholar 

  72. Ottonello L, Tortolina G, Amelotti M, Dallegri F (1999) Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes. J Immunol 162:3601–3606

    CAS  PubMed  Google Scholar 

  73. Phillips TA,, Ni J, Pan G, Ruben SM, Wei YF, Pace JL, Hunt JS (1999) TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege. J Immunol 162:6053–6059

    CAS  PubMed  Google Scholar 

  74. Rescigno M, Piguet V, Valzasina B, Lens S, Zubler R, French L, Kindler V, Tschopp J, Ricciardi-Castagnoli P (2000) Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses. J Exp Med 192:1661–1668

    Article  CAS  PubMed  Google Scholar 

  75. Restifo NP (2000) Not so Fas: re-evaluating the mechanisms of immune privilege and tumor escape. Nat Med 6:493–495

    CAS  PubMed  Google Scholar 

  76. Restifo NP (2001) Countering the ’counterattack’ hypothesis. Nat Med 7:259

    Article  CAS  PubMed  Google Scholar 

  77. Rogers AM, Boime I, Connolly J, Cook JR, Russell JH (1998) Maternal-fetal tolerance is maintained despite transgene-driven trophoblast expression of MHC class I, and defects in Fas and its ligand. Eur J Immunol 28:3479–3487

    Article  CAS  PubMed  Google Scholar 

  78. Saas P, Walker PR, Hahne M, Quiquerez AL, Schnuriger V, Perrin G, French L, Van Meir EG, de Tribolet N, Tschopp J, Dietrich PY (1997) Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain? J Clin Invest 99:1173–1178

    CAS  PubMed  Google Scholar 

  79. Sabelko KA, Kelly KA, Nahm MH, Cross AH, Russell JH (1997) Fas and Fas ligand enhance the pathogenesis of experimental allergic encephalomyelitis, but are not essential for immune privilege in the central nervous system. J Immunol 159:3096–3099

    CAS  PubMed  Google Scholar 

  80. Schmitz I, Kirchhoff S, Krammer PH (2000) Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol 32:1123–1136

    Article  CAS  PubMed  Google Scholar 

  81. Schmitz I, Krueger A, Baumann S, Schulze-Bergkamen H, Krammer PH, Kirchhoff S (2003) An IL-2-dependent switch between CD95 signaling pathways sensitizes primary human T cells toward CD95-mediated activation-induced cell death. J Immunol 171:2930–2936

    CAS  PubMed  Google Scholar 

  82. Seino K, Iwabuchi K, Kayagaki N, Miyata R, Nagaoka I, Matsuzawa A, Fukao K, Yagita H, Okumura K (1998) Chemotactic activity of soluble Fas ligand against phagocytes. J Immunol 161:4484–4488

    CAS  PubMed  Google Scholar 

  83. Seino K, Kayagaki N, Okumura K, Yagita H (1997) Antitumor effect of locally produced CD95 ligand. Nat Med 3:165–170

    Article  CAS  PubMed  Google Scholar 

  84. Shimizu M, Fontana A, Takeda Y, Yagita H, Yoshimoto T, Matsuzawa A. (1999) Induction of antitumor immunity with Fas/APO-1 ligand (CD95L)- transfected neuroblastoma neuro-2a cells. J Immunol 162:7350–7357

    CAS  PubMed  Google Scholar 

  85. Shudo K, Kinoshita K, Imamura R, Fan H, Hasumoto K, Tanaka M, Nagata S, Suda T (2001) The membrane-bound but not the soluble form of human Fas ligand is responsible for its inflammatory activity. Eur J Immunol 31:2504–2511

    Article  CAS  PubMed  Google Scholar 

  86. Simon AK, Gallimore A, Jones E, Sawitzki B, Cerundolo V, Screaton GR (2002) Fas ligand breaks tolerance to self-antigens and induces tumor immunity mediated by antibodies. Cancer Cell 2:315–322

    Article  CAS  PubMed  Google Scholar 

  87. Singh S, Ross SR., Acena M, Rowley DA, Schreiber H (1992) Stroma is critical for preventing or permitting immunological destruction of antigenic cancer cells. J Exp Med 175:139–146

    Article  CAS  PubMed  Google Scholar 

  88. Stahnke K, Fulda S, Friesen C, Strauss G, Debatin KM (2001) Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy. Blood 98:3066–3073

    Article  CAS  PubMed  Google Scholar 

  89. Strand S, Hofmann WJ, Hug H, Muller M, Otto G, Strand D, Mariani SM, Stremmel W, Krammer PH, Galle PR (1996) Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells—a mechanism of immune evasion?. Nat Med 2:1361–1366

    CAS  PubMed  Google Scholar 

  90. Strater J, Walczak H, Hasel C, Melzner I, Leithauser F, Moller P (2001) CD95 ligand (CD95L) immunohistochemistry: a critical study on 12 antibodies. Cell Death Differ 8:273–278

    Article  CAS  PubMed  Google Scholar 

  91. 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

    CAS  PubMed  Google Scholar 

  92. Tada Y, Wang JO, Takiguchi Y, Tatsumi K, Kuriyama T, Okada S, Tokuhisa T, Sakiyama S, Tagawa M. (2002) Cutting edge: a novel role for Fas ligand in facilitating antigen acquisition by dendritic cells. J Immunol 169:2241–2245

    CAS  PubMed  Google Scholar 

  93. Takeuchi T, Ueki T, Nishimatsu H, Kajiwara T, Ishida T, Jishage K, Ueda O, Suzuki H, Li B, Moriyama N, Kitamura T (1999) Accelerated rejection of Fas ligand-expressing heart grafts. J Immunol 162:518–522

    CAS  PubMed  Google Scholar 

  94. Walker PR, Saas P, Dietrich PY (1998) Tumor expression of Fas ligand (CD95L) and the consequences. Curr Opin Immunol 10:564–572

    Article  CAS  PubMed  Google Scholar 

  95. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992) Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317

    Article  CAS  PubMed  Google Scholar 

  96. Yagita H, Seino K, Kayagaki N, Okumura K (1996) CD95 ligand in graft rejection. Nature 379:682

    Article  CAS  PubMed  Google Scholar 

  97. Yolcu ES, Askenasy N, Singh NP, Cherradi SE, Shirwan H (2002) Cell membrane modification for rapid display of proteins as a novel means of immunomodulation: FasL-decorated cells prevent islet graft rejection. Immunity 17:795–808

    Article  CAS  PubMed  Google Scholar 

  98. Zamzami N, Kroemer G (2001) The mitochondrion in apoptosis: how Pandora’s box opens. Nat Rev Mol Cell Biol 2:67–71

    Article  CAS  PubMed  Google Scholar 

  99. Zhang HG, Fleck M, Kern ER, Liu D, Wang Y, Hsu HC, Yang P, Wang Z, Curiel DT, Zhou T, Mountz JD (2000) Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand-deficient mice. J Clin Invest 105:813–821

    CAS  PubMed  Google Scholar 

  100. Zhang HG, Su X, Liu D, Liu W, Yang P, Wang Z, Edwards CK, Bluethmann H, Mountz JD, Zhou T (1999) Induction of specific T cell tolerance by Fas ligand-expressing antigen-presenting cells. J Immunol 162:1423–1430

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Frederik H. Igney

    Present address: Schering AG, CRBA Dermatology, Muellerstr. 178, 13342, Berlin, Germany

Authors and Affiliations

  1. Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Frederik H. Igney & Peter H. Krammer

Authors
  1. Frederik H. Igney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter H. Krammer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frederik H. Igney.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Igney, F.H., Krammer, P.H. Tumor counterattack: fact or fiction?. Cancer Immunol Immunother 54, 1127–1136 (2005). https://doi.org/10.1007/s00262-005-0680-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-005-0680-7

Keywords

Search

Navigation