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Miscellaneous

Cell-based therapy approaches using dying cells: from tumour immunotherapy to transplantation tolerance induction

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Pages 249-263 | Published online: 23 Feb 2005

Bibliography

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  • •• This paper is an extensive review of the different receptors involved in apoptotic cell uptake.
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  • •• Matzinger defined ‘danger’ as the major signal influencing immune response. Her viewpoint has refreshed tumour and transplantation immunology.
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  • •• An elegant illustration of the interaction between cell death, immunogenicity and tumourigenicity. As mentioned in the title, inhibition of apoptosis prevents immunogenicity, suggesting that tumour apoptosis in vivo is necessary to generate immune response. In their following article (see [106]), these authors suggest that tumour apoptotic materials are taken by phagocytes and guided to draining lymph nodes.
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  • • This paper describes autoantibody production following massive infusion of apoptotic syngeneic thymocytes. The authors propose that an excess of apoptosis prone to autoimmunity. The results are a little bit overestimated when compared to mice genetically prone to lupus. However, the concept is very interesting.
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  • •• Macrophages have the capacity to modulate the immune response after apoptotic cell uptake. This may be an additional security to avoid autoimmunity. The following papers of this team [28,67] are also very convincing and allow defining the role of macrophage as keeper of peripheral tolerance. See [24].
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  • •• See [26]. This paper describes the characterisation of the PS R.
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  • •• This is an interesting comment about receptors involved in apoptotic cell uptake and the subsequent signalling pathways.
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  • •• An extensive review on DCs.
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  • •• A summary of the different functions and lineages of DCs.
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  • •• This paper is critical for tumour immunotherapy using DCs as adjuvants. Indeed, iDCs are responsible for tolerance induction. In contrast, this is an interesting approach to test in transplantation.
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  • • This paper gives more information on the role of DCs on tolerance.
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  • • Mammalian DNA can cause DC maturation. This suggests that released DNA can be a ‘danger’ signal in the absence of quick removal or degradation.
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  • •• This fascinating paper provides an additional mechanism for peripheral tolerance. A subpopulation of DCs may be dedicated to capture antigens from apoptotic normal tissue in the periphery and to inactivate self-antigen reactive T-lymphocytes in lymph node.
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  • • A receptor involved in apoptotic cell uptake is also capable to inhibit DC maturation. This concept is interesting and will certainly generate more studies on this aspect.
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  • • See [60–62].
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  • • See [59, 61, 62].
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  • • See [59–62].
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  • • See [59-61]. Some acute phase proteins have the capacities to bind apoptotic cells and to modify the capture of such cells. In general, these acute phase proteins have an anti-inflammatory effect that prevents unwanted efficient immune response.
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  • • This elegant article describes a new clearance pathway for apoptotic cells. A complex associating different partners (apoptotic cell, the first protein of the complement C1q and a soluble protein calreticulin) interacts with the receptor in fashion, CD91. Indeed, this receptor is also the receptor for Hsps.
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  • • This is one of the initial papers describing DC maturation following necrotic tumour cells. In contrast, necrotic cells from normal tissues do not induce such maturation.
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  • •• In 1998, this paper stimulated the authors not to consider apoptosis as a cell death mechanism ignored by the adaptive immune system. It was also novel for them that cell death is not just a mechanism to stop an immune response (AICD for example). In addition, physiological apoptotic cell death has to be distinguished from accidental necrosis. The role of Hsps in immunogenicity is elegantly addressed using the suicide gene approach. See [76].
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  • • This is the second part of the story ‘heat shock protein and immunogenicity’, see [75].
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  • • Here, the authors describe an interesting link between a ‘dangerous’ cell death mechanism necrosis and a family of ‘danger’ receptors, namely the TLRs.
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  • • This is the third part of the story ‘heat shock proteins, stress and immunogenicity’. See [75,76].
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  • •• Expression of stimulating molecules (here, CD40L) by apoptotic cells induces DC maturation. This adds a level of complexity. Before this paper, it was sufficient to dissociate normal tissue and tumour. Now, the differentiation stage of a similar cell may influence the outcome.
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  • DE CARVALHO BITTENCOURT M, PERRUCHE S, CONTASSOT E et al: Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers. Blood (2001) 98(1):224–230.
  • •• This paper addresses for the first time the use of apoptotic cells for tolerance induction. The immunomodulatory properties of apoptotic cells are used to inhibit host immune response. Some questions are still arising, such as the involved mechanism.
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  • SCAFFIDI C, FULDA S, SRINIVASAN A et al: Two CD95 (APO-1/Fas) signaling pathways. EMBO J. (1998) 17(6): 1675–1687.
  • BELLONE M: Apoptosis, cross-presentation, and the fate of the antigen specific immune response. Apoptosis (2000) 5 (4): 307–314.
  • •• An interesting review discussing the immunogenicity of apoptotic cells. The authors propose that the pro-apoptotic stimulus may influence apoptotic cell uptake, protein degradation, peptide trafficking, peptide association with MHC molecules and finally antigen presentation. This is a way to explore.
  • PACZESNY S, BERANGER S, SALZMANN JL, KLATZMANN D, COLOMBO BM: Protection of mice against leukemia after vaccination with bone marrow-derived dendritic cells loaded with apoptotic leukemia cells. Cancer Res. (2001) 61(6):2386–2389.
  • BERARD F, BLANCO P, DAVOUST J et al: Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells. J. Exp. Med. (2000) 192(11):1535–1544.
  • JENNE L, ARRIGHI JF, JONULEIT H, SAURAT JH, HAUSER C: Dendritic cells containing apoptotic melanoma cells prime human CD8+ T cells for efficient tumor cell lysis. Cancer Res. (2000) 60(16):4446–4452.
  • RUSSO V, TANZARELLA S, DALERBA P et al.: Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response. Proc. Natl. Acad. Sci. USA (2000) 97(5):2185–2190.
  • SHAIF-MUTHANA M, MCINTYRE C, SISLEY K, RENNIE I, MURRAY A: Dead or alive: immunogenicity of human melanoma cells when presented by dendritic cells. Cancer Res. (2000) 60(22):6441–6447.
  • CHATTERGOON MA, KIM JJ, YANG JS et al.: Targeted antigen delivery to antigen-presenting cells including dendritic cells by engineered Fas-mediated apoptosis. Nat. Biotechnol. (2000) 18(9):974–979. This paper elegantly demonstrates that favouring APC apoptosis increases antigen transfer and immunogenicity.
  • HENRY F, BRETAUDEAU L, BARBIEUX I, MEFLAH K, GREGOIRE M: Induction of antigen presentation by macrophages after phagocytosis of tumour apoptotic cells. Res. Immunol. (1998) 149(7-8):673–679.
  • HEATH WR, CARBONE FR: Cross-presentation, dendritic cells, tolerance and immunity. Ann. Rev. Immunol. (2001) 19:47–64.
  • ••This is a brilliant review on cross-presentation and cross-tolerance.
  • RENZ A, BERDEL WE, KREUTER M, BELKA C, SCHULZE-OSTHOFF K, LOS M: Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo. Blood (2001) 98(5):1542–1548.
  • BARKER FG, DAVIS RL, CHANG SM, PRADOS MD: Necrosis as a prognostic factor in glioblastoma multiforme. Cancer (1996) 77(6):1161–1166.
  • BONNOTTE B, FAVRE N, MOUTET M et al.: Role of tumor cell apoptosis in tumor antigen migration to the draining lymph nodes. J. Immunol. (2000) 164(4):1995–2000.
  • ••See [16].
  • BERGER CL, XU AL, HANLON D et al.: Induction of human tumor-loaded dendritic cells. Int. J. Cancer. (2001) 91 (4): 438-447.
  • BONNOTTE B, LARMONIER N, FAVRE N et al: Identification of tumor-infiltrating macrophages as the killers of tumor cells after immunization in a rat model system. J. Immunol. (2001) 167(9) :5077–5083.
  • LUDEWIG B, MCCOY K, PERICIN M et al: Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells. J. Immunol. (2001) 166(6): 3678–3687.
  • FUJITA N, KAGAMU H, YOSHIZAWA H et al: CD40 Ligand promotes priming of fully potent antitumor CD4(+) T cells in draining lymph nodes in the presence of apoptotic tumor cells. J. Immunol. (2001) 167(10) :5678–5 688.
  • •• This paper is interesting in two aspects. Firstly, it confirms that apoptotic cells alone are not a good approach to vaccine against tumour. Secondly, it also excludes necrosis as a sufficient ‘danger’ signal. In contrast, CD40L expressing viable tumour cells in a limited amount are sufficient to prime antitumour specific T-cells.
  • HIRAO M, ONAI N, HIROISHI K et al.: CC chemokine receptor-7 on dendritic cells is induced after interaction with apoptotic tumor cells: critical role in migration from the tumor site to draining lymph nodes. Cancer Res. (2000) 60(8):2209–2217.
  • RUSSO V, ZHOU D, SARTIRANA C et al: Acquisition of intact allogeneic human leukocyte antigen molecules by human dendritic cells. Blood (2000) 95(11):3473–3477.
  • • See [113].
  • HARSHYNE LA, WATKINS SC, GAMBOTTO A, BARRATT-BOYES SM: Dendritic cells acquire antigens from live cells for cross-presentation to CTL. J. Immunol. (2001) 166(6):3717–3723. Published Erratum in J. Immunol. (2001) 166(9):5840.
  • • These two papers [112,113] are disconcerting, but also very interesting. In a very provocative manner, they make us ask the question about the necessity to use dying tumour cells to favour antitumour immune response. Indeed, non-replicative tumour cells have been previously reported [13] as the most efficient approach to generate antitumour immune response.
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