Impact of Tumour Cell Death on the Activation of Anti-tumour Immune Response

  • Jiřina Bartůňková
  • Radek Špíšek


The primary function of the immune system is to protect the host against pathogens. Success of vaccination against infectious diseases has led to efforts to develop strategies to activate a specific immune response against cancer. However, this task has proved to be very challenging. In the last few years there has been rapid progress in the identification of the molecular mechanisms by which the immune system detects pathogens and initiates immune responses. By contrast, recognition of neoplastic cells lags behind, and induction of specific anti-tumour immunity is even less understood. In this chapter we discuss evidence for the role of the immune system in the control of tumour growth. We also review recent advances in the understanding of mechanisms that can alert the immune system to the presence of neoplastic lesions, and we discuss recent data on the immunogenicity of tumour cells and their interaction with antigen presenting cells.

Cancer immune-editing Dendritic cells Heat shock proteins Immunogenicity of tumour cells Immunotherapy Tumour immunology 


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  1. Ada G (2001) Vaccines and vaccination. N Engl J Med 345:1042–1053PubMedCrossRefGoogle Scholar
  2. Ada GL (1990) The immunological principles of vaccination. Lancet 335:523–526PubMedCrossRefGoogle Scholar
  3. Adema GJ, de Vries IJ, Punt CJ et al (2005) Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol 17:170–174PubMedCrossRefGoogle Scholar
  4. Albert ML, Darnell JC, Bender A et al (1998) Tumour-specific killer cells in paraneoplastic cerebellar degeneration. Nat Med 4:1321–1324PubMedCrossRefGoogle Scholar
  5. Albert ML, Darnell RB (2004) Paraneoplastic neurological degenerations: keys to tumour immunity. Nat Rev Cancer 4:36–44PubMedCrossRefGoogle Scholar
  6. Apetoh L, Ghiringhelli F, Tesniere A et al (2007a) Toll-like receptor 4-dependent contribution of the immune system to anti-cancer chemotherapy and radiotherapy. Nat Med 13:1050–1059CrossRefGoogle Scholar
  7. Apetoh L, Obeid M, Tesniere A et al (2007b) Immunogenic chemotherapy: discovery of a critical protein through proteomic analyses of tumour cells. Cancer Genomics Proteomics 4:65–70Google Scholar
  8. Arispe N, Doh M, Simakova O et al (2004) Hsc70 and Hsp70 interact with phosphatidylserine on the surface of PC12 cells resulting in a decrease of viability. FASEB J 18:1636–1645PubMedCrossRefGoogle Scholar
  9. Bach EA, Aguet M, Schreiber RD (1997) The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 15:563–591PubMedCrossRefGoogle Scholar
  10. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252PubMedCrossRefGoogle Scholar
  11. Bartkova J, Horejsi Z, Koed K et al (2005) DNA damage response as a candidate anti-cancer barrier in early human tumourigenesis. Nature 434:864–870PubMedCrossRefGoogle Scholar
  12. Basu S, Binder RJ, Ramalingam T et al (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313PubMedCrossRefGoogle Scholar
  13. Basu S, Binder RJ, Suto R et al (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 12:1539–1546PubMedCrossRefGoogle Scholar
  14. Becker T, Hartl FU, Wieland F (2002) CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol 158:1277–1285PubMedCrossRefGoogle Scholar
  15. Beere HM, Wolf BB, Cain K et al (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469–475PubMedCrossRefGoogle Scholar
  16. Bender A, Sapp M, Schuler G et al (1996) Improved methods for the generation of dendritic cells from non-proliferating progenitors in human blood. J Immunol Methods 196:121–135PubMedCrossRefGoogle Scholar
  17. Binder RJ, Anderson KM, Basu S et al (2000a) Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo. J Immunol 165:6029–6035Google Scholar
  18. Binder RJ, Han DK, Srivastava PK (2000b) CD91: a receptor for heat shock protein gp96. Nat Immunol 1:151–155CrossRefGoogle Scholar
  19. Binder RJ, Harris ML, Menoret A et al (2000c) Saturation, competition, and specificity in interaction of heat shock proteins (hsp) gp96, hsp90, and hsp70 with CD11b+ cells. J Immunol 165:2582–2587Google Scholar
  20. Binder RJ, Kelly JB, 3rd, Vatner RE et al (2007) Specific immunogenicity of heat shock protein gp96 derives from chaperoned antigenic peptides and not from contaminating proteins. J Immunol 179:7254–7261PubMedGoogle Scholar
  21. Binder RJ, Srivastava PK (2004) Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci U S A 101:6128–6133PubMedCrossRefGoogle Scholar
  22. Binder RJ, Srivastava PK (2005) Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+ T cells. Nat Immunol 6:593–599PubMedCrossRefGoogle Scholar
  23. Burdelya L, Kujawski M, Niu G et al (2005) Stat3 activity in melanoma cells affects migration of immune effector cells and nitric oxide-mediated anti-tumour effects. J Immunol 174:3925–3931PubMedGoogle Scholar
  24. Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumour Res 13:1–27Google Scholar
  25. Bushley AW, Ferrell R, McDuffie K et al (2004) Polymorphisms of interleukin (IL)-1alpha, IL- 1beta, IL-6, IL-10, and IL-18 and the risk of ovarian cancer. Gynecol Oncol 95:672–679PubMedCrossRefGoogle Scholar
  26. Casares N, Pequignot MO, Tesniere A et al (2005) Caspase-dependent immunogenicity of doxorubicin- induced tumour cell death. J Exp Med 202:1691–1701PubMedCrossRefGoogle Scholar
  27. Castedo M, Perfettini JL, Roumier T et al (2004a) Cell death by mitotic catastrophe: a molecular definition. Oncogene 23:2825–2837CrossRefGoogle Scholar
  28. Castedo M, Perfettini JL, Roumier T et al (2004b) Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy. Oncogene 23:4362–4370CrossRefGoogle Scholar
  29. Castedo M, Perfettini JL, Roumier T et al (2004c) The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe. Oncogene 23:4353–4361CrossRefGoogle Scholar
  30. Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949PubMedCrossRefGoogle Scholar
  31. Curiel TJ, Wei S, Dong H et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated anti-tumour immunity. Nat Med 9:562–567PubMedCrossRefGoogle Scholar
  32. Dai J, Liu B, Caudill MM et al (2003) Cell surface expression of heat shock protein gp96 enhances cross-presentation of cellular antigens and the generation of tumour-specific T cell memory. Cancer Immun 3:1PubMedGoogle Scholar
  33. Darnell RB, Posner JB (2003a) Observing the invisible: successful tumour immunity in humans. Nat Immunol 4:201CrossRefGoogle Scholar
  34. Darnell RB, Posner JB (2003b) Paraneoplastic syndromes involving the nervous system. N Engl J Med 349:1543–1554CrossRefGoogle Scholar
  35. De Vries IJ, Bernsen MR, van Geloof WL et al (2007) In situ detection of antigen-specific T cells in cryo-sections using MHC class I tetramers after dendritic cell vaccination of melanoma patients. Cancer Immunol Immunother 56:1667–1676PubMedCrossRefGoogle Scholar
  36. Demaria S, Santori FR, Ng B et al (2005) Select forms of tumour cell apoptosis induce dendritic cell maturation. J Leukoc Biol 77:361–368PubMedCrossRefGoogle Scholar
  37. Dhodapkar MV (2005) Harnessing host immune responses to preneoplasia: promise and challenges. Cancer Immunol Immunother 54:409–413PubMedCrossRefGoogle Scholar
  38. Dhodapkar MV, Bhardwaj N (2000) Active immunization of humans with dendritic cells. J Clin Immunol 20:167–174PubMedCrossRefGoogle Scholar
  39. Dhodapkar MV, Dhodapkar KM, Palucka AK (2008) Interactions of tumour cells with dendritic cells: balancing immunity and tolerance. Cell Death Differ 15:39–50PubMedCrossRefGoogle Scholar
  40. Dhodapkar MV, Krasovsky J, Olson K (2002) T cells from the tumour microenvironment of patients with progressive myeloma can generate strong, tumour-specific cytolytic responses to autologous, tumour-loaded dendritic cells. Proc Natl Acad Sci U S A 99:13009–13013PubMedCrossRefGoogle Scholar
  41. Dhodapkar MV, Krasovsky J, Osman K et al (2003) Vigorous premalignancy-specific effector T cell response in the bone marrow of patients with monoclonal gammopathy. J Exp Med 198:1753–1757PubMedCrossRefGoogle Scholar
  42. Dhodapkar MV, Steinman RM (2002) Antigen-bearing immature dendritic cells induce peptidespecific CD8(+) regulatory T cells in vivo in humans. Blood 100:174–177PubMedCrossRefGoogle Scholar
  43. Dhodapkar MV, Steinman RM, Krasovsky J et al (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238PubMedCrossRefGoogle Scholar
  44. Dighe AS, Richards E, Old LJ et al (1994) Enhanced in vivo growth and resistance to rejection of tumour cells expressing dominant negative IFN gamma receptors. Immunity 1:447–456PubMedCrossRefGoogle Scholar
  45. Dunn GP, Bruce AT, Ikeda H et al (2002) Cancer immunoediting: from immunosurveillance to tumour escape. Nat Immunol 3:991–998PubMedCrossRefGoogle Scholar
  46. Dunn GP, Old LJ, Schreiber RD (2004a) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148CrossRefGoogle Scholar
  47. Dunn GP, Old LJ, Schreiber RD (2004b) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–360CrossRefGoogle Scholar
  48. Edwards AD, Manickasingham SP, Sporri R et al (2002) Microbial recognition via Toll-like receptor- dependent and -independent pathways determines the cytokine response of murine dendritic cell subsets to CD40 triggering. J Immunol 169:3652–3660PubMedGoogle Scholar
  49. Fadok VA, Bratton DL, Guthrie L et al (2001) Differential effects of apoptotic vs. lysed cells on macrophage production of cytokines: role of proteases. J Immunol 166:6847–6854PubMedGoogle Scholar
  50. Figdor CG, de Vries IJ, Lesterhuis WJ et al (2004) Dendritic cell immunotherapy: mapping the ay. Nat Med 10:475–480PubMedCrossRefGoogle Scholar
  51. Frenzel H, Hoffmann B, Brocks C et al (2006) Toll-like receptor interference in myeloid dendritic cells through head and neck cancer. Anticancer Res 26:4409–4413PubMedGoogle Scholar
  52. Galluzzi L, Maiuri MC, Vitale I et al (2007) Cell death modalities: classification and pathophysiological implications. Cell Death Differ 14:1237–1243PubMedCrossRefGoogle Scholar
  53. Gardai SJ, Bratton DL, Ogden CA et al (2006) Recognition ligands on apoptotic cells: a perspective. J Leukocyte Biol 79:896–903PubMedCrossRefGoogle Scholar
  54. Garrido C, Fromentin A, Bonnotte B et al (1998) Heat shock protein 27 enhances the tumourigenicity of immunogenic rat colon carcinoma cell clones. Cancer Res 58:5495–5499PubMedGoogle Scholar
  55. Gasser S, Orsulic S, Brown EJ et al (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190PubMedCrossRefGoogle Scholar
  56. Gerecitano J, Goy A, Wright J et al (2006) Drug-induced cutaneous vasculitis in patients with non-Hodgkin lymphoma treated with the novel proteasome inhibitor bortezomib: a possible surrogate marker of response? Br J Haematol 134:391–398PubMedCrossRefGoogle Scholar
  57. Gilboa E (2004) The promise of cancer vaccines. Nat Rev Cancer 4:401–411PubMedCrossRefGoogle Scholar
  58. Gorgoulis VG, Vassiliou LV, Karakaidos P et al (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434:907–913PubMedCrossRefGoogle Scholar
  59. Hayakawa Y, Takeda K, Yagita H et al (2002) IFN-gamma-mediated inhibition of tumour angiogenesis by natural killer T-cell ligand, alpha-galactosylceramide. Blood 100:1728–1733PubMedGoogle Scholar
  60. Hung K, Hayashi R, Lafond-Walker A et al (1998) The central role of CD4(+) T cells in the antitumour immune response. J Exp Med 188:2357–2368PubMedCrossRefGoogle Scholar
  61. Cheng F, Wang HW, Cuenca A et al (2003) A critical role for Stat3 signaling in immune tolerance. Immunity 19:425–436PubMedCrossRefGoogle Scholar
  62. Ishii KJ, Suzuki K, Coban C et al (2001) Genomic DNA released by dying cells induces the maturation of APCs. J Immunol 167:2602–2607PubMedGoogle Scholar
  63. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995PubMedCrossRefGoogle Scholar
  64. Jaattela M (1995) Over-expression of hsp70 confers tumourigenicity to mouse fibrosarcoma cells. Int J Cancer 60:689–693PubMedCrossRefGoogle Scholar
  65. Janeway CA, Jr., Goodnow CC, Medzhitov R (1996) Danger - pathogen on the premises! Immunological tolerance. Curr Biol 6:519–522PubMedCrossRefGoogle Scholar
  66. Kaplan DH, Shankaran V, Dighe AS et al (1998) Demonstration of an interferon gamma-dependent tumour surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A 95:7556–7561PubMedCrossRefGoogle Scholar
  67. Kroemer G, El-Deiry WS, Golstein P et al (2005) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ 12 Suppl 2:1463–1467CrossRefGoogle Scholar
  68. Krysko DV, D’Herde K, Vandenabeele P (2006) Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11:1709–1726PubMedCrossRefGoogle Scholar
  69. Krysko DV, Leybaert L, Vandenabeele P et al (2005) Gap junctions and the propagation of cell survival and cell death signals. Apoptosis 10:459–469PubMedCrossRefGoogle Scholar
  70. Kyle RA, Rajkumar SV (1999) Monoclonal gammopathies of undetermined significance. Hematol Oncol Clin North Am 13:1181–1202PubMedCrossRefGoogle Scholar
  71. Labarriere N, Bretaudeau L, Gervois N et al (2002) Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T lymphocytes specific for NA17-A antigen but not for Melan- A/MART-1 antigen. Int J Cancer 101:280–286PubMedCrossRefGoogle Scholar
  72. Lech-Maranda E, Baseggio L, Bienvenu J et al (2004) Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. Blood 103:3529–3534PubMedCrossRefGoogle Scholar
  73. Liyanage UK, Moore TT, Joo HG et al (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumour microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169:2756–2761PubMedGoogle Scholar
  74. Lollini PL, Cavallo F, Nanni P et al (2006) Vaccines for tumour prevention. Nat Rev Cancer 6:204–216PubMedCrossRefGoogle Scholar
  75. Lollini PL, De Giovanni C, Pannellini T et al (2005) Cancer immunoprevention. Future Oncol 1:57–66PubMedCrossRefGoogle Scholar
  76. Lollini PL, Forni G (2002) Anti-tumour vaccines: is it possible to prevent a tumour? Cancer Immunol Immunother 51:409–416Google Scholar
  77. Lollini PL, Forni G (2003) Cancer immunoprevention: tracking down persistent tumour antigens. Trends Immunol 24:62–66PubMedCrossRefGoogle Scholar
  78. Maiuri MC, Zalckvar E, Kimchi A et al (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752PubMedCrossRefGoogle Scholar
  79. Marincola FM, Jaffee EM, Hicklin DJ et al (2000) Escape of human solid tumours from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 74:181–273PubMedCrossRefGoogle Scholar
  80. Martinon F, Petrilli V, Mayor A et al (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241PubMedCrossRefGoogle Scholar
  81. Masse D, Ebstein F, Bougras G et al (2004) Increased expression of inducible HSP70 in apoptotic cells is correlated with their efficacy for anti-tumour vaccine therapy. Int J Cancer 111:575–583PubMedCrossRefGoogle Scholar
  82. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145PubMedCrossRefGoogle Scholar
  83. Medzhitov R, Janeway C, Jr. (2000a) Innate immune recognition: mechanisms and pathways. Immunol Rev 173:89–97CrossRefGoogle Scholar
  84. Medzhitov R, Janeway C, Jr. (2000b) Innate immunity. N Engl J Med 343:338–344CrossRefGoogle Scholar
  85. Medzhitov R, Janeway CA, Jr. (1997a) Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 9:4–9CrossRefGoogle Scholar
  86. Medzhitov R, Janeway CA, Jr. (1997b) Innate immunity: the virtues of a non-clonal system of recognition. Cell 91:295–298CrossRefGoogle Scholar
  87. Mumberg D, Monach PA, Wanderling S et al (1999) CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc Natl A cad Sci U S A 96:8633–8638CrossRefGoogle Scholar
  88. Obeid M, Tesniere A, Ghiringhelli F et al (2007a) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefGoogle Scholar
  89. Obeid M, Tesniere A, Panaretakis T et al (2007b) Ecto-calreticulin in immunogenic chemotherapy. Immunol Rev 220:22–34CrossRefGoogle Scholar
  90. Pardoll DM (1998) Cancer vaccines. Nat Med 4:525–531PubMedCrossRefGoogle Scholar
  91. Park JS, Gamboni-Robertson F, He Q et al (2006) High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Physiol Cell Physiol 290:C917–C924PubMedCrossRefGoogle Scholar
  92. Park JS, Svetkauskaite D, He Q et al (2004) Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279:7370–7377PubMedCrossRefGoogle Scholar
  93. Pasare C, Medzhitov R (2004a) Toll-like receptors and acquired immunity. Semin Immunol 16:23–26CrossRefGoogle Scholar
  94. Pasare C, Medzhitov R (2004b) Toll-like receptors: linking innate and adaptive immunity. Microbes Infect 6:1382–1387CrossRefGoogle Scholar
  95. Reis e Sousa C, Diebold SD, Edwards AD et al (2003) Regulation of dendritic cell function by microbial stimuli. Pathol Biol (Paris) 51:67–68Google Scholar
  96. Rock KL, Hearn A, Chen et al (2005) Natural endogenous adjuvants. Springer Semin Immunopathol 26:231–246PubMedCrossRefGoogle Scholar
  97. Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909–915PubMedCrossRefGoogle Scholar
  98. Rovere-Querini P, Capobianco A, Scaffidi P et al (2004) HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 5:825–830PubMedCrossRefGoogle Scholar
  99. Sauter B, Albert ML, Francisco L et al (2000) Consequences of cell death: exposure to necrotic tumour cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191:423–434PubMedCrossRefGoogle Scholar
  100. Savill J, Dransfield I, Gregory C et al (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975PubMedCrossRefGoogle Scholar
  101. Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407:784–788PubMedCrossRefGoogle Scholar
  102. Savill J, Fadok V, Henson P et al (1993) Phagocyte recognition of cells undergoing apoptosis. Immunol Today 14:131–136PubMedCrossRefGoogle Scholar
  103. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195PubMedCrossRefGoogle Scholar
  104. Shankaran V, Ikeda H, Bruce AT et al (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111PubMedCrossRefGoogle Scholar
  105. Shi H, Cao T, Connolly JE et al (2006) Hyperthermia enhances CTL cross-priming. J Immunol 176:2134–2141PubMedGoogle Scholar
  106. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521PubMedCrossRefGoogle Scholar
  107. Shi Y, Rock KL (2002) Cell death releases endogenous adjuvants that selectively enhance immune surveillance of particulate antigens. Eur J Immunol 32:155–162PubMedCrossRefGoogle Scholar
  108. Shinkai Y, Rathbun G, Lam KP et al (1992) RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68:855–867PubMedCrossRefGoogle Scholar
  109. Shortman K, Liu YJ (2002) Mouse and human dendritic cell subtypes. Nat Rev Immunol 2:151–161PubMedCrossRefGoogle Scholar
  110. Scheibner KA, Lutz MA, Boodoo S et al (2006) Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol 177:1272–1281PubMedGoogle Scholar
  111. Schnurr M, Scholz C, Rothenfusser S et al (2002) Apoptotic pancreatic tumour cells are superior to cell lysates in promoting cross-priming of cytotoxic T cells and activate NK and gammadelta T cells. Cancer Res 62:2347–2352PubMedGoogle Scholar
  112. Singh-Jasuja H, Toes RE, Spee P et al (2000) Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis. J Exp Med 191:1965–1974PubMedCrossRefGoogle Scholar
  113. Smyth MJ, Crowe NY, Godfrey DI (2001) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459–463PubMedCrossRefGoogle Scholar
  114. Smyth MJ, Thia KY, Street SE et al (2000) Differential tumour surveillance by natural killer (NK) and NKT cells. J Exp Med 191:661–668PubMedCrossRefGoogle Scholar
  115. Somersan S, Larsson M, Fonteneau JF et al (2001) Primary tumour tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells. J Immunol 167:4844–4852PubMedGoogle Scholar
  116. Spisek R (2006) Immunoprevention of cancer: time to reconsider timing of vaccination against cancer. Expert Rev Anticancer Ther 6:1689–1691PubMedCrossRefGoogle Scholar
  117. Spisek R, Brazova J, Rozkova D et al (2004) Maturation of dendritic cells by bacterial immunomodulators. Vaccine 22:2761–2768PubMedCrossRefGoogle Scholar
  118. Spisek R, Dhodapkar MV (2006) Immunoprevention of cancer. Hematol Oncol Clin North Am 20:735–750PubMedCrossRefGoogle Scholar
  119. Spisek R, Charalambous A, Mazumder A et al (2007) Bortezomib enhances dendritic cell (DC) mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumour cells: therapeutic implications. BloodGoogle Scholar
  120. Spisek R, Chevallier P, Morineau N et al (2002) Induction of leukemia-specific cytotoxic response by cross-presentation of late-apoptotic leukemic blasts by autologous dendritic cells of nonleukemic origin. Cancer Res 62:2861–2868PubMedGoogle Scholar
  121. Sporri R, Reis e Sousa C (2005) Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol 6:163–170PubMedCrossRefGoogle Scholar
  122. Steinman RM, Banchereau J (2007) Taking dendritic cells into medicine. Nature 449:419–426PubMedCrossRefGoogle Scholar
  123. Steinman RM, Bonifaz L, Fujii S et al (2005) The innate functions of dendritic cells in peripheral lymphoid tissues. Adv Exp Med Biol 560:83–97PubMedCrossRefGoogle Scholar
  124. Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumour initiation, growth, and metastasis. Blood 97:192–197PubMedCrossRefGoogle Scholar
  125. Stutman O (1975) Immunodepression and malignancy. Adv Cancer Res 22:261–422PubMedCrossRefGoogle Scholar
  126. Tacken PJ, de Vries IJ, Torensma R et al (2007) Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 7:790–802PubMedCrossRefGoogle Scholar
  127. Tesniere A, Panaretakis T, Kepp O et al (2008) Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 15:3–12PubMedCrossRefGoogle Scholar
  128. Tobiasova Z, Pospisilova D, Miller AM et al (2007) In vitro assessment of dendritic cells pulsed with apoptotic tumour cells as a vaccine for ovarian cancer patients. Clin Immunol 122:18–27PubMedCrossRefGoogle Scholar
  129. Udono H, Srivastava PK (1993) Heat shock protein 70-associated peptides elicit specific cancer immunity. J Exp Med 178:1391–1396PubMedCrossRefGoogle Scholar
  130. Uyttenhove C, Pilotte L, Theate I et al (2003) Evidence for a tumoural immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9:1269–1274PubMedCrossRefGoogle Scholar
  131. Van Den Broek ME, Kagi D, Ossendorp F et al (1996) Decreased tumour surveillance in perforindeficient mice. J Exp Med 184:1781–1790PubMedCrossRefGoogle Scholar
  132. Verdijk P, Scheenen TW, Lesterhuis WJ et al (2007) Sensitivity of magnetic resonance imaging of dendritic cells for in vivo tracking of cellular cancer vaccines. Int J Cancer 120:978–984PubMedCrossRefGoogle Scholar
  133. Walport MJ (2000) Lupus, DNase and defective disposal of cellular debris. Nat Genet 25:135–136PubMedCrossRefGoogle Scholar
  134. Wang H, Bloom O, Zhang M et al (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251PubMedCrossRefGoogle Scholar
  135. Wang HY, Lee DA, Peng G et al (2004a) Tumour-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20:107–118CrossRefGoogle Scholar
  136. Wang T, Niu G, Kortylewski M et al (2004b) Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumour cells. Nat Med 10:48–54CrossRefGoogle Scholar
  137. Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146PubMedCrossRefGoogle Scholar
  138. Winau F, Weber S, Sad S et al (2006) Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity 24:105–117PubMedCrossRefGoogle Scholar
  139. Wong LH, Krauer KG, Hatzinisiriou I et al (1997) Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma. J Biol Chem 272:28779–28785PubMedCrossRefGoogle Scholar
  140. Woo EY, Chu CS, Goletz TJ et al (2001) Regulatory CD4(+)CD25(+) T cells in tumours from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61:4766–4772PubMedGoogle Scholar
  141. Yamazaki S, Bonito AJ, Spisek R et al (2007) Dendritic cells are specialized accessory cells along with TGF-{beta} for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3- precursors. BloodGoogle Scholar
  142. Zaft T, Sapoznikov A, Krauthgamer R et al (2005) CD11chigh dendritic cell ablation impairs lymphopenia- driven proliferation of naive and memory CD8+ T cells. J Immunol 175:6428–6435PubMedGoogle Scholar
  143. Zitvogel L, Apetoh L, Ghiringhelli F et al (2008) Immunological aspects of cancer chemotherapy. Nat Rev Immunol 8:59–73PubMedCrossRefGoogle Scholar
  144. Zitvogel L, Casares N, Pequignot MO et al (2004) Immune response against dying tumour cells. Adv Immunol 84:131–179PubMedCrossRefGoogle Scholar
  145. Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6:715–727PubMedCrossRefGoogle Scholar
  146. Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6:295–307PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jiřina Bartůňková
    • 1
  • Radek Špíšek
    • 1
  1. 1.Department of ImmunologyCharles University, Second Medical School University Hospital MotolCzech Republic

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