Advertisement

Apoptosis

, Volume 14, Issue 4, pp 364–375 | Cite as

Immunogenic cell death modalities and their impact on cancer treatment

  • Oliver Kepp
  • Antoine Tesniere
  • Frederic Schlemmer
  • Mickael Michaud
  • Laura Senovilla
  • Laurence Zitvogel
  • Guido Kroemer
Cell Death and Disease

Abstract

It is still enigmatic under which circumstances cellular demise induces an immune response or rather remains immunologically silent. Moreover, the question remains open under which circumstances apoptotic, autophagic or necrotic cells are immunogenic or tolerogenic. Although apoptosis appears to be morphologically homogenous, recent evidence suggests that the pre-apoptotic surface-exposure of calreticulin may dictate the immune response to tumor cells that succumb to anticancer treatments. Moreover, the release of high-mobility group box 1 (HMGB1) during late apoptosis and secondary necrosis contributes to efficient antigen presentation and cytotoxic T-cell activation because HMGB1 can bind to Toll like receptor 4 on dendritic cells, thereby stimulating optimal antigen processing. Cell death accompanied by autophagy also may facilitate cross priming events. Apoptosis, necrosis and autophagy are closely intertwined processes. Often, cells manifest autophagy before they undergo apoptosis or necrosis, and apoptosis is generally followed by secondary necrosis. Whereas apoptosis and necrosis irreversibly lead to cell death, autophagy can clear cells from stress factors and thus facilitate cellular survival. We surmise that the response to cellular stress like chemotherapy or ionizing irradiation, dictates the immunological response to dying cells and that this immune response in turn determines the clinical outcome of anticancer therapies. The purpose of this review is to summarize recent insights into the immunogenicity of dying tumor cells as a function of the cell death modality.

Keywords

Cell death Calreticulin Cancer immunity 

Notes

Acknowledgments

G.K. is supported by a special grant from Ligue contre le Cancer (équipe labellisée) as well as by grants from European Commission (Active p53, AICR, RIGHT, Trans-Death, Death-Train, ChemoRes) and by Institut National contre le Cancer (INCa). O.K. receives a long term fellowship from EMBO, A.T is supported by INSERM. F.S. is supported by Fondation pour la recherché Medical, L.S. is supported by Death Train Network.

References

  1. 1.
    Obeid M, Tesniere A, Ghiringhelli F et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61. doi: 10.1038/nm1523 PubMedCrossRefGoogle Scholar
  2. 2.
    Apetoh L, Ghiringhelli F, Tesniere A et al (2007) The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol Rev 220:47–59. doi: 10.1111/j.1600-065X.2007.00573.x PubMedCrossRefGoogle Scholar
  3. 3.
    Apetoh L, Ghiringhelli F, Tesniere A et al (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059. doi: 10.1038/nm1622 PubMedCrossRefGoogle Scholar
  4. 4.
    Zitvogel L, Apetoh L, Ghiringhelli F, Andre F, Tesniere A, Kroemer G (2008) The anticancer immune response: indispensable for therapeutic success? J Clin Invest 118:1991–2001. doi: 10.1172/JCI35180 PubMedCrossRefGoogle Scholar
  5. 5.
    Zitvogel L, Kroemer G (2008) The immune response against dying tumor cells: avoid disaster, achieve cure. Cell Death Differ 15:1–2. doi: 10.1038/sj.cdd.4402267 PubMedCrossRefGoogle Scholar
  6. 6.
    Panaretakis T, Joza N, Modjtahedi N et al (2008) The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death. Cell Death Differ 15:1499–1509. doi: 10.1038/cdd.2008.67 PubMedCrossRefGoogle Scholar
  7. 7.
    Tufi R, Panaretakis T, Bianchi K et al (2008) Reduction of endoplasmic reticulum Ca2+ levels favors plasma membrane surface exposure of calreticulin. Cell Death Differ 15:274–282. doi: 10.1038/sj.cdd.4402275 PubMedCrossRefGoogle Scholar
  8. 8.
    Zitvogel L, Casares N, Pequignot MO, Chaput N, Albert ML, Kroemer G (2004) Immune response against dying tumor cells. Adv Immunol 84:131–179. doi: 10.1016/S0065-2776(04)84004-5 PubMedCrossRefGoogle Scholar
  9. 9.
    Acosta JC, O’Loghlen A, Banito A et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133:1006–1018. doi: 10.1016/j.cell.2008.03.038 PubMedCrossRefGoogle Scholar
  10. 10.
    Kuilman T, Michaloglou C, Vredeveld LC et al (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133:1019–1031. doi: 10.1016/j.cell.2008.03.039 PubMedCrossRefGoogle Scholar
  11. 11.
    Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR (2008) Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132:363–374. doi: 10.1016/j.cell.2007.12.032 PubMedCrossRefGoogle Scholar
  12. 12.
    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):1463–1467. doi: 10.1038/sj.cdd.4401724 PubMedCrossRefGoogle Scholar
  13. 13.
    Galluzzi L, Maiuri MC, Vitale I et al (2007) Cell death modalities: classification and pathophysiological implications. Cell Death Differ 14:1237–1243. doi: 10.1038/sj.cdd.4402148 PubMedCrossRefGoogle Scholar
  14. 14.
    Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedGoogle Scholar
  15. 15.
    Kroemer G, Martin SJ (2005) Caspase-independent cell death. Nat Med 11:725–730. doi: 10.1038/nm1263 PubMedCrossRefGoogle Scholar
  16. 16.
    Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163. doi: 10.1152/physrev.00013.2006 PubMedCrossRefGoogle Scholar
  17. 17.
    Ferri KF, Kroemer G (2001) Mitochondria—the suicide organelles. Bioessays 23:111–115. doi:10.1002/1521-1878(200102)23:2<111::AID-BIES1016>3.0.CO;2-YPubMedCrossRefGoogle Scholar
  18. 18.
    Marzo I, Susin SA, Petit PX et al (1998) Caspases disrupt mitochondrial membrane barrier function. FEBS Lett 427:198–202. doi: 10.1016/S0014-5793(98)00424-4 PubMedCrossRefGoogle Scholar
  19. 19.
    Oda E, Ohki R, Murasawa H et al (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053–1058. doi: 10.1126/science.288.5468.1053 PubMedCrossRefGoogle Scholar
  20. 20.
    Ley R, Balmanno K, Hadfield K, Weston C, Cook SJ (2003) Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim. J Biol Chem 278:18811–18816. doi: 10.1074/jbc.M301010200 PubMedCrossRefGoogle Scholar
  21. 21.
    Ley R, Ewings KE, Hadfield K, Howes E, Balmanno K, Cook SJ (2004) Extracellular signal-regulated kinases 1/2 are serum-stimulated “Bim(EL) kinases” that bind to the BH3-only protein Bim(EL) causing its phosphorylation and turnover. J Biol Chem 279:8837–8847. doi: 10.1074/jbc.M311578200 PubMedCrossRefGoogle Scholar
  22. 22.
    Zong WX, Lindsten T, Ross AJ, MacGregor GR, Thompson CB (2001) BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev 15:1481–1486. doi: 10.1101/gad.897601 PubMedCrossRefGoogle Scholar
  23. 23.
    Wei MC, Lindsten T, Mootha VK et al (2000) tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14:2060–2071PubMedGoogle Scholar
  24. 24.
    Schulze-Osthoff K, Krammer PH, Droge W (1994) Divergent signalling via APO-1/Fas and the TNF receptor, two homologous molecules involved in physiological cell death. EMBO J 13:4587–4596PubMedGoogle Scholar
  25. 25.
    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. doi: 10.1038/375081a0 PubMedCrossRefGoogle Scholar
  26. 26.
    Savill J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975. doi: 10.1038/nri957 PubMedCrossRefGoogle Scholar
  27. 27.
    Chen W, Frank ME, Jin W, Wahl SM (2001) TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 14:715–725. doi: 10.1016/S1074-7613(01)00147-9 PubMedCrossRefGoogle Scholar
  28. 28.
    Fournier T, Fadok V, Henson PM (1997) Tumor necrosis factor-alpha inversely regulates prostaglandin D2 and prostaglandin E2 production in murine macrophages. Synergistic action of cyclic AMP on cyclooxygenase-2 expression and prostaglandin E2 synthesis. J Biol Chem 272:31065–31072. doi: 10.1074/jbc.272.49.31065 PubMedCrossRefGoogle Scholar
  29. 29.
    Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407:784–788. doi: 10.1038/35037722 PubMedCrossRefGoogle Scholar
  30. 30.
    Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351. doi: 10.1038/37022 PubMedCrossRefGoogle Scholar
  31. 31.
    Casares N, Pequignot MO, Tesniere A et al (2005) Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 202:1691–1701. doi: 10.1084/jem.20050915 PubMedCrossRefGoogle Scholar
  32. 32.
    Obeid M, Panaretakis T, Joza N et al (2007) Calreticulin exposure is required for the immunogenicity of gamma-irradiation and UVC light-induced apoptosis. Cell Death Differ 14:1848–1850. doi: 10.1038/sj.cdd.4402201 PubMedCrossRefGoogle Scholar
  33. 33.
    Obeid M, Panaretakis T, Tesniere A et al (2007) Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from “silent” to immunogenic. Cancer Res 67:7941–7944. doi: 10.1158/0008-5472.CAN-07-1622 PubMedCrossRefGoogle Scholar
  34. 34.
    Albert ML, Pearce SF, Francisco LM et al (1998) Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188:1359–1368. doi: 10.1084/jem.188.7.1359 PubMedCrossRefGoogle Scholar
  35. 35.
    Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89. doi: 10.1038/32183 PubMedCrossRefGoogle Scholar
  36. 36.
    Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252. doi: 10.1038/32588 PubMedCrossRefGoogle Scholar
  37. 37.
    Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752. doi: 10.1038/nrm2239 PubMedCrossRefGoogle Scholar
  38. 38.
    Boya P, Gonzalez-Polo RA, Casares N et al (2005) Inhibition of macroautophagy triggers apoptosis. Mol Cell Biol 25:1025–1040. doi: 10.1128/MCB.25.3.1025-1040.2005 PubMedCrossRefGoogle Scholar
  39. 39.
    Furuya N, Yu J, Byfield M, Pattingre S, Levine B (2005) The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1:46–52PubMedGoogle Scholar
  40. 40.
    Amaravadi RK, Thompson CB (2007) The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin Cancer Res 13:7271–7279. doi: 10.1158/1078-0432.CCR-07-1595 PubMedCrossRefGoogle Scholar
  41. 41.
    Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8:275–283. doi: 10.1038/nrm2147 PubMedCrossRefGoogle Scholar
  42. 42.
    Feng Z, Zhang H, Levine AJ, Jin S (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci USA 102:8204–8209. doi: 10.1073/pnas.0502857102 PubMedCrossRefGoogle Scholar
  43. 43.
    Xue W, Zender L, Miething C et al (2007) Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445:656–660. doi: 10.1038/nature05529 PubMedCrossRefGoogle Scholar
  44. 44.
    Amaravadi RK, Yu D, Lum JJ et al (2007) Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 117:326–336. doi: 10.1172/JCI28833 PubMedCrossRefGoogle Scholar
  45. 45.
    Tasdemir E, Maiuri MC, Galluzzi L et al (2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10:676–687. doi: 10.1038/ncb1730 PubMedCrossRefGoogle Scholar
  46. 46.
    Gonzalez-Polo RA, Boya P, Pauleau AL et al (2005) The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci 118:3091–3102. doi: 10.1242/jcs.02447 PubMedCrossRefGoogle Scholar
  47. 47.
    Shimizu S, Kanaseki T, Mizushima N et al (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6:1221–1228. doi: 10.1038/ncb1192 PubMedCrossRefGoogle Scholar
  48. 48.
    Degenhardt K, Mathew R, Beaudoin B et al (2006) Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 10:51–64. doi: 10.1016/j.ccr.2006.06.001 PubMedCrossRefGoogle Scholar
  49. 49.
    Qu X, Zou Z, Sun Q et al (2007) Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128:931–946. doi: 10.1016/j.cell.2006.12.044 PubMedCrossRefGoogle Scholar
  50. 50.
    Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753–766. doi: 10.1016/j.cell.2004.11.038 PubMedCrossRefGoogle Scholar
  51. 51.
    Paludan C, Schmid D, Landthaler M et al (2005) Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307:593–596. doi: 10.1126/science.1104904 PubMedCrossRefGoogle Scholar
  52. 52.
    Dengjel J, Schoor O, Fischer R et al (2005) Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA 102:7922–7927. doi: 10.1073/pnas.0501190102 PubMedCrossRefGoogle Scholar
  53. 53.
    Uhl M, Kepp O, Jusforgues-Saklani H, Vicencio JM, Kroemer G, Albert ML (2009) Autophagy within the antigen donor cell facilitates efficient antigen cross-priming. Cell Death Differ (accepted)Google Scholar
  54. 54.
    Edinger AL, Thompson CB (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16:663–669. doi: 10.1016/j.ceb.2004.09.011 PubMedCrossRefGoogle Scholar
  55. 55.
    Roach HI, Clarke NM (2000) Physiological cell death of chondrocytes in vivo is not confined to apoptosis. New observations on the mammalian growth plate. J Bone Joint Surg Br 82:601–613. doi: 10.1302/0301-620X.82B4.9846 Google Scholar
  56. 56.
    Barkla DH, Gibson PR (1999) The fate of epithelial cells in the human large intestine. Pathology 31:230–238. doi: 10.1080/003130299105043 PubMedCrossRefGoogle Scholar
  57. 57.
    Holler N, Zaru R, Micheau O et al (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1:489–495. doi: 10.1038/82732 PubMedCrossRefGoogle Scholar
  58. 58.
    Temkin V, Huang Q, Liu H, Osada H, Pope RM (2006) Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis. Mol Cell Biol 26:2215–2225. doi: 10.1128/MCB.26.6.2215-2225.2006 PubMedCrossRefGoogle Scholar
  59. 59.
    Nicotera P, Leist M, Ferrando-May E (1998) Intracellular ATP, a switch in the decision between apoptosis and necrosis. Toxicol Lett 102–103:139–142. doi: 10.1016/S0378-4274(98)00298-7 PubMedCrossRefGoogle Scholar
  60. 60.
    Golstein P, Kroemer G (2005) Redundant cell death mechanisms as relics and backups. Cell Death Differ 12(Suppl. 2):1490–1496. doi: 10.1038/sj.cdd.4401607 PubMedCrossRefGoogle Scholar
  61. 61.
    Chautan M, Chazal G, Cecconi F, Gruss P, Golstein P (1999) Interdigital cell death can occur through a necrotic and caspase-independent pathway. Curr Biol 9:967–970. doi: 10.1016/S0960-9822(99)80425-4 PubMedCrossRefGoogle Scholar
  62. 62.
    Krysko DV, Denecker G, Festjens N et al (2006) Macrophages use different internalization mechanisms to clear apoptotic and necrotic cells. Cell Death Differ 13:2011–2022. doi: 10.1038/sj.cdd.4401900 PubMedCrossRefGoogle Scholar
  63. 63.
    Vakkila J, Lotze MT (2004) Inflammation and necrosis promote tumour growth. Nat Rev Immunol 4:641–648. doi: 10.1038/nri1415 PubMedCrossRefGoogle Scholar
  64. 64.
    Fadok VA, Bratton DL, Guthrie L, Henson PM (2001) Differential effects of apoptotic versus lysed cells on macrophage production of cytokines: role of proteases. J Immunol 166:6847–6854PubMedGoogle Scholar
  65. 65.
    Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195. doi: 10.1038/nature00858 PubMedCrossRefGoogle Scholar
  66. 66.
    Wang H, Bloom O, Zhang M et al (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251. doi: 10.1126/science.285.5425.248 PubMedCrossRefGoogle Scholar
  67. 67.
    Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R, Kroemer G (2004) Cell death by mitotic catastrophe: a molecular definition. Oncogene 23:2825–2837. doi: 10.1038/sj.onc.1207528 PubMedCrossRefGoogle Scholar
  68. 68.
    Kops GJ, Weaver BA, Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5:773–785. doi: 10.1038/nrc1714 PubMedCrossRefGoogle Scholar
  69. 69.
    Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636. doi: 10.1016/0014-4827(65)90211-9 PubMedCrossRefGoogle Scholar
  70. 70.
    Campisi J (2007) d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8:729–740. doi: 10.1038/nrm2233 PubMedCrossRefGoogle Scholar
  71. 71.
    Itahana K, Campisi J, Dimri GP (2007) Methods to detect biomarkers of cellular senescence: the senescence-associated beta-galactosidase assay. Methods Mol Biol 371:21–31. doi: 10.1007/978-1-59745-361-5_3 PubMedCrossRefGoogle Scholar
  72. 72.
    Kurz T, Terman A, Brunk UT (2007) Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron. Arch Biochem Biophys 462:220–230. doi: 10.1016/j.abb.2007.01.013 PubMedCrossRefGoogle Scholar
  73. 73.
    van Heemst D, den Reijer PM, Westendorp RG (2007) Ageing or cancer: a review on the role of caretakers and gatekeepers. Eur J Cancer 43:2144–2152. doi: 10.1016/j.ejca.2007.07.011 PubMedCrossRefGoogle Scholar
  74. 74.
    Di Leonardo A, Linke SP, Clarkin K, Wahl GM (1994) DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev 8:2540–2551. doi: 10.1101/gad.8.21.2540 PubMedCrossRefGoogle Scholar
  75. 75.
    Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14:501–513. doi: 10.1016/S1097-2765(04)00256-4 PubMedCrossRefGoogle Scholar
  76. 76.
    Vicencio JM, Galluzzi L, Tajeddine N et al (2008) Senescence, apoptosis or autophagy? When a damaged cell must decide its path—a mini-review. Gerontology 54:92–99. doi: 10.1159/000129697 PubMedCrossRefGoogle Scholar
  77. 77.
    Helmbold H, Deppert W, Bohn W (2006) Regulation of cellular senescence by Rb2/p130. Oncogene 25:5257–5262. doi: 10.1038/sj.onc.1209613 PubMedCrossRefGoogle Scholar
  78. 78.
    Vaziri H, Benchimol S (1999) Alternative pathways for the extension of cellular life span: inactivation of p53/pRb and expression of telomerase. Oncogene 18:7676–7680. doi: 10.1038/sj.onc.1203016 PubMedCrossRefGoogle Scholar
  79. 79.
    Kapic A, Helmbold H, Reimer R, Klotzsche O, Deppert W, Bohn W (2006) Cooperation between p53 and p130(Rb2) in induction of cellular senescence. Cell Death Differ 13:324–334. doi: 10.1038/sj.cdd.4401756 PubMedCrossRefGoogle Scholar
  80. 80.
    Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602. doi: 10.1016/S0092-8674(00)81902-9 PubMedCrossRefGoogle Scholar
  81. 81.
    Lowe SW, Cepero E, Evan G (2004) Intrinsic tumour suppression. Nature 432:307–315. doi: 10.1038/nature03098 PubMedCrossRefGoogle Scholar
  82. 82.
    Narita M, Lowe SW (2005) Senescence comes of age. Nat Med 11:920–922. doi: 10.1038/nm0905-920 PubMedCrossRefGoogle Scholar
  83. 83.
    Gardai SJ, McPhillips KA, Frasch SC et al (2005) Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 123:321–334. doi: 10.1016/j.cell.2005.08.032 PubMedCrossRefGoogle Scholar
  84. 84.
    Chaput N, De Botton S, Obeid M et al (2007) Molecular determinants of immunogenic cell death: surface exposure of calreticulin makes the difference. J Mol Med 85:1069–1076. doi: 10.1007/s00109-007-0214-1 PubMedCrossRefGoogle Scholar
  85. 85.
    Ogden CA, de Cathelineau A, Hoffmann PR et al (2001) C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med 194:781–795. doi: 10.1084/jem.194.6.781 PubMedCrossRefGoogle Scholar
  86. 86.
    Berwin B, Delneste Y, Lovingood RV, Post SR, Pizzo SV (2004) SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J Biol Chem 279:51250–51257. doi: 10.1074/jbc.M406202200 PubMedCrossRefGoogle Scholar
  87. 87.
    Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C (2007) Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 81:15–27. doi: 10.1189/jlb.0306167 PubMedCrossRefGoogle Scholar
  88. 88.
    Saito K, Dai Y, Ohtsuka K (2005) Enhanced expression of heat shock proteins in gradually dying cells and their release from necrotically dead cells. Exp Cell Res 310:229–236. doi: 10.1016/j.yexcr.2005.07.014 PubMedCrossRefGoogle Scholar
  89. 89.
    Asea A, Kraeft SK, Kurt-Jones EA et al (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442. doi: 10.1038/74697 PubMedCrossRefGoogle Scholar
  90. 90.
    Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (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 12:1539–1546. doi: 10.1093/intimm/12.11.1539 PubMedCrossRefGoogle Scholar
  91. 91.
    Jaattela M (1995) Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells. Int J Cancer 60:689–693. doi: 10.1002/ijc.2910600520 PubMedCrossRefGoogle Scholar
  92. 92.
    Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR, Kaul SC (2002) Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res 274:246–253. doi: 10.1006/excr.2002.5468 PubMedCrossRefGoogle Scholar
  93. 93.
    Ravagnan L, Gurbuxani S, Susin SA et al (2001) Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol 3:839–843. doi: 10.1038/ncb0901-839 PubMedCrossRefGoogle Scholar
  94. 94.
    Lee JS, Lee JJ, Seo JS (2005) HSP70 deficiency results in activation of c-Jun N-terminal Kinase, extracellular signal-regulated kinase, and caspase-3 in hyperosmolarity-induced apoptosis. J Biol Chem 280:6634–6641. doi: 10.1074/jbc.M412393200 PubMedCrossRefGoogle Scholar
  95. 95.
    Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (1999) NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature 401:82–85. doi: 10.1038/43466 PubMedCrossRefGoogle Scholar
  96. 96.
    Spisek R, Charalambous A, Mazumder A, Vesole DH, Jagannath S, Dhodapkar MV (2007) Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications. Blood 109:4839–4845. doi: 10.1182/blood-2006-10-054221 PubMedCrossRefGoogle Scholar
  97. 97.
    Thorburn J, Horita H, Redzic J, Hansen K, Frankel AE, Thorburn A (2008) Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. Cell Death Differ 16:175–183PubMedCrossRefGoogle Scholar
  98. 98.
    Kazama H, Ricci JE, Herndon JM, Hoppe G, Green DR, Ferguson TA (2008) Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29:21–32. doi: 10.1016/j.immuni.2008.05.013 PubMedCrossRefGoogle Scholar
  99. 99.
    Tesniere A, Apetoh L, Ghiringhelli F et al (2008) Immunogenic cancer cell death: a key-lock paradigm. Curr Opin Immunol 20:504–511. doi: 10.1016/j.coi.2008.05.007 PubMedCrossRefGoogle Scholar
  100. 100.
    Haynes NM, van der Most RG, Lake RA, Smyth MJ (2008) Immunogenic anti-cancer chemotherapy as an emerging concept. Curr Opin Immunol 20:545–557. doi: 10.1016/j.coi.2008.05.008 PubMedCrossRefGoogle Scholar
  101. 101.
    Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190. doi: 10.1038/nature03884 PubMedCrossRefGoogle Scholar
  102. 102.
    Guerra N, Tan YX, Joncker NT et al (2008) NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28:571–580. doi: 10.1016/j.immuni.2008.02.016 PubMedCrossRefGoogle Scholar
  103. 103.
    Bauer S, Groh V, Wu J et al (1999) Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729. doi: 10.1126/science.285.5428.727 PubMedCrossRefGoogle Scholar
  104. 104.
    Kariko K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 279:12542–12550. doi: 10.1074/jbc.M310175200 PubMedCrossRefGoogle Scholar
  105. 105.
    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
  106. 106.
    Krysko DV, Leybaert L, Vandenabeele P, D’Herde K (2005) Gap junctions and the propagation of cell survival and cell death signals. Apoptosis 10:459–469. doi: 10.1007/s10495-005-1875-2 PubMedCrossRefGoogle Scholar
  107. 107.
    Ferrari D, Wesselborg S, Bauer MK, Schulze-Osthoff K (1997) Extracellular ATP activates transcription factor NF-kappaB through the P2Z purinoreceptor by selectively targeting NF-kappaB p65. J Cell Biol 139:1635–1643. doi: 10.1083/jcb.139.7.1635 PubMedCrossRefGoogle Scholar
  108. 108.
    Bottazzi B, Garlanda C, Salvatori G, Jeannin P, Manfredi A, Mantovani A (2006) Pentraxins as a key component of innate immunity. Curr Opin Immunol 18:10–15. doi: 10.1016/j.coi.2005.11.009 PubMedCrossRefGoogle Scholar
  109. 109.
    Kepp O, Tesniere A, Zitvogel L, Kroemer G (2009) The immunogenicity of tumor cell death. Curr Opin Oncol (accepted)Google Scholar
  110. 110.
    Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305. doi: 10.1126/science.1071059 PubMedCrossRefGoogle Scholar
  111. 111.
    Li M, Carpio DF, Zheng Y et al (2001) An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J Immunol 166:7128–7135PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Oliver Kepp
    • 1
    • 2
    • 3
  • Antoine Tesniere
    • 1
    • 2
    • 3
  • Frederic Schlemmer
    • 1
    • 2
    • 3
  • Mickael Michaud
    • 1
    • 2
    • 3
  • Laura Senovilla
    • 1
    • 2
    • 3
  • Laurence Zitvogel
    • 2
    • 3
    • 4
    • 5
  • Guido Kroemer
    • 1
    • 2
    • 3
  1. 1.INSERM, U848VillejuifFrance
  2. 2.Institut Gustave RoussyVillejuifFrance
  3. 3.Université Paris-Sud 11VillejuifFrance
  4. 4.INSERM, U805VillejuifFrance
  5. 5.CIC BT507VillejuifFrance

Personalised recommendations