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01-11-2011 | Original article

Poly(I:C)-induced tumour cell death leads to DC maturation and Th1 activation

Published in: Cancer Immunology, Immunotherapy | Issue 11/2011

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Abstract

Dendritic cells (DCs) have the ability to generate peptide epitopes for MHC class I molecules derived from apoptotic tumour cells for direct recognition by cytotoxic T cells. This function has lead to DCs being used in vaccine strategies. In this study, we investigate the effect of inducing apoptosis in tumour cell lines using IFN-γ and poly(I:C), the subsequent maturation of the endocytosing DC and its ability to direct the resulting T cell response. We show that uptake of poly(I:C)-induced apoptotic tumour cells leads to DC maturation and activation with a Th1 cell polarising capacity. In contrast, these effects are not seen by DCs loaded with γ-irradiated apoptotic tumour cells. We propose that the manner in which tumour cells are induced to die can have a profound effect on the endocytosing DC and the resulting T cell response.
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Literature
2.
go back to reference Kurosaka K, Takahashi M, Watanabe N, Kobayashi Y (2003) Silent cleanup of very early apoptotic cells by macrophages. J Immunol 171:4672–4679PubMed Kurosaka K, Takahashi M, Watanabe N, Kobayashi Y (2003) Silent cleanup of very early apoptotic cells by macrophages. J Immunol 171:4672–4679PubMed
3.
go back to reference Savill J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975PubMedCrossRef Savill J, Dransfield I, Gregory C, Haslett C (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2:965–975PubMedCrossRef
4.
go back to reference Pietra G, Mortarini R, Parmiani G, Anichini A (2001) Phases of apoptosis of melanoma cells, but not of normal melanocytes, differently affect maturation of myeloid dendritic cells. Cancer Res 61:8218–8226PubMed Pietra G, Mortarini R, Parmiani G, Anichini A (2001) Phases of apoptosis of melanoma cells, but not of normal melanocytes, differently affect maturation of myeloid dendritic cells. Cancer Res 61:8218–8226PubMed
5.
go back to reference Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898PubMedCrossRef Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890–898PubMedCrossRef
6.
go back to reference Jacobs BL, Langland JO (1996) When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. Virology 219:339–349PubMedCrossRef Jacobs BL, Langland JO (1996) When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA. Virology 219:339–349PubMedCrossRef
7.
go back to reference Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738PubMedCrossRef Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738PubMedCrossRef
8.
go back to reference Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105PubMedCrossRef Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105PubMedCrossRef
9.
go back to reference Meusel TR, Kehoe KE, Imani F (2002) Protein kinase R regulates double-stranded RNA induction of TNF-alpha but not IL-1 beta mRNA in human epithelial cells. J Immunol 168:6429–6435PubMed Meusel TR, Kehoe KE, Imani F (2002) Protein kinase R regulates double-stranded RNA induction of TNF-alpha but not IL-1 beta mRNA in human epithelial cells. J Immunol 168:6429–6435PubMed
10.
go back to reference Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27:3135–3142PubMedCrossRef Jonuleit H, Kuhn U, Muller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27:3135–3142PubMedCrossRef
11.
12.
go back to reference Sallusto F, Cella M, Danieli C, Lanzavecchia A (1995) Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med 182:389–400PubMedCrossRef Sallusto F, Cella M, Danieli C, Lanzavecchia A (1995) Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med 182:389–400PubMedCrossRef
13.
go back to reference Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, Bhardwaj N (1998) Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188:1359–1368PubMedCrossRef Albert ML, Pearce SF, Francisco LM, Sauter B, Roy P, Silverstein RL, Bhardwaj N (1998) Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188:1359–1368PubMedCrossRef
14.
go back to reference Rubartelli A, Poggi A, Zocchi MR (1997) The selective engulfment of apoptotic bodies by dendritic cells is mediated by the alpha(v)beta3 integrin and requires intracellular and extracellular calcium. Eur J Immunol 27:1893–1900PubMedCrossRef Rubartelli A, Poggi A, Zocchi MR (1997) The selective engulfment of apoptotic bodies by dendritic cells is mediated by the alpha(v)beta3 integrin and requires intracellular and extracellular calcium. Eur J Immunol 27:1893–1900PubMedCrossRef
15.
go back to reference Skoberne M, Somersan S, Almodovar W, Truong T, Petrova K, Henson PM, Bhardwaj N (2006) The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human dendritic-cell immunostimulatory function. Blood 108:947–955PubMedCrossRef Skoberne M, Somersan S, Almodovar W, Truong T, Petrova K, Henson PM, Bhardwaj N (2006) The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human dendritic-cell immunostimulatory function. Blood 108:947–955PubMedCrossRef
16.
go back to reference Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89PubMedCrossRef Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89PubMedCrossRef
17.
go back to reference Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811PubMedCrossRef Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811PubMedCrossRef
18.
go back to reference van Wilsem EJ, Breve J, Kleijmeer M, Kraal G (1994) Antigen-bearing Langerhans cells in skin draining lymph nodes: phenotype and kinetics of migration. J Invest Dermatol 103:217–220PubMedCrossRef van Wilsem EJ, Breve J, Kleijmeer M, Kraal G (1994) Antigen-bearing Langerhans cells in skin draining lymph nodes: phenotype and kinetics of migration. J Invest Dermatol 103:217–220PubMedCrossRef
19.
go back to reference Blander JM (2007) Signalling and phagocytosis in the orchestration of host defence. Cell Microbiol 9:290–299PubMedCrossRef Blander JM (2007) Signalling and phagocytosis in the orchestration of host defence. Cell Microbiol 9:290–299PubMedCrossRef
20.
go back to reference Kapsenberg ML, Hilkens CM, Wierenga EA, Kalinski P (1999) The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy. Clin Exp Allergy 29(Suppl 2):33–36PubMedCrossRef Kapsenberg ML, Hilkens CM, Wierenga EA, Kalinski P (1999) The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy. Clin Exp Allergy 29(Suppl 2):33–36PubMedCrossRef
21.
go back to reference Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 117:433–442PubMedCrossRef Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 117:433–442PubMedCrossRef
22.
go back to reference Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238PubMedCrossRef Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238PubMedCrossRef
23.
go back to reference Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G (2002) Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 195:1279–1288PubMedCrossRef Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G (2002) Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 195:1279–1288PubMedCrossRef
24.
go back to reference Moller I, Michel K, Frech N, Burger M, Pfeifer D, Frommolt P, Veelken H, Thomas-Kaskel AK (2008) Dendritic cell maturation with poly(I:C)-based versus PGE2-based cytokine combinations results in differential functional characteristics relevant to clinical application. J Immunother 31:506–519PubMedCrossRef Moller I, Michel K, Frech N, Burger M, Pfeifer D, Frommolt P, Veelken H, Thomas-Kaskel AK (2008) Dendritic cell maturation with poly(I:C)-based versus PGE2-based cytokine combinations results in differential functional characteristics relevant to clinical application. J Immunother 31:506–519PubMedCrossRef
25.
go back to reference Verdijk RM, Mutis T, Esendam B, Kamp J, Melief CJ, Brand A, Goulmy E (1999) Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol 163:57–61PubMed Verdijk RM, Mutis T, Esendam B, Kamp J, Melief CJ, Brand A, Goulmy E (1999) Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol 163:57–61PubMed
26.
go back to reference Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179:1109–1118PubMedCrossRef Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179:1109–1118PubMedCrossRef
27.
go back to reference Bender A, Sapp M, Schuler G, Steinman RM, Bhardwaj N (1996) Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. J Immunol Methods 196:121–135PubMedCrossRef Bender A, Sapp M, Schuler G, Steinman RM, Bhardwaj N (1996) Improved methods for the generation of dendritic cells from nonproliferating progenitors in human blood. J Immunol Methods 196:121–135PubMedCrossRef
28.
go back to reference Reis e Sousa C, Diebold SD, Edwards AD, Rogers N, Schulz O, Sporri R (2003) Regulation of dendritic cell function by microbial stimuli. Pathol Biol (Paris) 51:67–68CrossRef Reis e Sousa C, Diebold SD, Edwards AD, Rogers N, Schulz O, Sporri R (2003) Regulation of dendritic cell function by microbial stimuli. Pathol Biol (Paris) 51:67–68CrossRef
29.
go back to reference Mailliard RB, Wankowicz-Kalinska A, Cai Q, Wesa A, Hilkens CM, Kapsenberg ML, Kirkwood JM, Storkus WJ, Kalinski P (2004) Alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res 64:5934–5937PubMedCrossRef Mailliard RB, Wankowicz-Kalinska A, Cai Q, Wesa A, Hilkens CM, Kapsenberg ML, Kirkwood JM, Storkus WJ, Kalinski P (2004) Alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res 64:5934–5937PubMedCrossRef
30.
go back to reference Restifo NP (2000) Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity. Curr Opin Immunol 12:597–603PubMedCrossRef Restifo NP (2000) Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity. Curr Opin Immunol 12:597–603PubMedCrossRef
31.
go back to reference Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61PubMedCrossRef Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van Endert P, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61PubMedCrossRef
32.
go back to reference Medzhitov R, Janeway CA Jr (2000) How does the immune system distinguish self from nonself? Semin Immunol 12:185–188 (discussion 257–344)PubMedCrossRef Medzhitov R, Janeway CA Jr (2000) How does the immune system distinguish self from nonself? Semin Immunol 12:185–188 (discussion 257–344)PubMedCrossRef
33.
go back to reference Ullrich E, Bonmort M, Mignot G, Kroemer G, Zitvogel L (2008) Tumor stress, cell death and the ensuing immune response. Cell Death Differ 15:21–28PubMedCrossRef Ullrich E, Bonmort M, Mignot G, Kroemer G, Zitvogel L (2008) Tumor stress, cell death and the ensuing immune response. Cell Death Differ 15:21–28PubMedCrossRef
34.
go back to reference Stevanovic S (2002) Identification of tumour-associated T-cell epitopes for vaccine development. Nat Rev Cancer 2:514–520PubMedCrossRef Stevanovic S (2002) Identification of tumour-associated T-cell epitopes for vaccine development. Nat Rev Cancer 2:514–520PubMedCrossRef
35.
go back to reference Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296–306PubMedCrossRef Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296–306PubMedCrossRef
36.
go back to reference Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4:328–332PubMedCrossRef Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4:328–332PubMedCrossRef
37.
go back to reference Redman BG, Chang AE, Whitfield J, Esper P, Jiang G, Braun T, Roessler B, Mule JJ (2008) Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma. J Immunother 31:591–598PubMedCrossRef Redman BG, Chang AE, Whitfield J, Esper P, Jiang G, Braun T, Roessler B, Mule JJ (2008) Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma. J Immunother 31:591–598PubMedCrossRef
38.
go back to reference Adams M, Navabi H, Jasani B, Man S, Fiander A, Evans AS, Donninger C, Mason M (2003) Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21:787–790PubMedCrossRef Adams M, Navabi H, Jasani B, Man S, Fiander A, Evans AS, Donninger C, Mason M (2003) Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21:787–790PubMedCrossRef
39.
go back to reference O’Rourke MG, Johnson MK, Lanagan CM, See JL, O’Connor LE, Slater GJ, Thomas D, Lopez JA, Martinez NR, Ellem KA, Schmidt CW (2007) Dendritic cell immunotherapy for stage IV melanoma. Melanoma Res 17:316–322PubMedCrossRef O’Rourke MG, Johnson MK, Lanagan CM, See JL, O’Connor LE, Slater GJ, Thomas D, Lopez JA, Martinez NR, Ellem KA, Schmidt CW (2007) Dendritic cell immunotherapy for stage IV melanoma. Melanoma Res 17:316–322PubMedCrossRef
40.
go back to reference Delirezh N, Moazzeni SM, Shokri F, Shokrgozar MA, Atri M, Kokhaei P (2009) Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro. Cell Immunol 257:23–31PubMedCrossRef Delirezh N, Moazzeni SM, Shokri F, Shokrgozar MA, Atri M, Kokhaei P (2009) Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro. Cell Immunol 257:23–31PubMedCrossRef
41.
go back to reference Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, Kroemer G, Martin F, Chauffert B, Zitvogel L (2005) Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+ CD25+ regulatory T cell proliferation. J Exp Med 202:919–929PubMedCrossRef Ghiringhelli F, Puig PE, Roux S, Parcellier A, Schmitt E, Solary E, Kroemer G, Martin F, Chauffert B, Zitvogel L (2005) Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+ CD25+ regulatory T cell proliferation. J Exp Med 202:919–929PubMedCrossRef
42.
go back to reference Russo V, Tanzarella S, Dalerba P, Rigatti D, Rovere P, Villa A, Bordignon C, Traversari C (2000) 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 97:2185–2190PubMedCrossRef Russo V, Tanzarella S, Dalerba P, Rigatti D, Rovere P, Villa A, Bordignon C, Traversari C (2000) 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 97:2185–2190PubMedCrossRef
43.
go back to reference Goldszmid RS, Idoyaga J, Bravo AI, Steinman R, Mordoh J, Wainstok R (2003) Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol 171:5940–5947PubMed Goldszmid RS, Idoyaga J, Bravo AI, Steinman R, Mordoh J, Wainstok R (2003) Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol 171:5940–5947PubMed
44.
go back to reference Kovalcsik E, John J, Turner M, Birchall L, Sage D, Whittle R, Dalgleish A, Pandha H (2004) Differential expression of melanoma-associated antigens and molecules involved in antigen processing and presentation in three cell lines established from a single patient. Melanoma Res 14:463–471PubMedCrossRef Kovalcsik E, John J, Turner M, Birchall L, Sage D, Whittle R, Dalgleish A, Pandha H (2004) Differential expression of melanoma-associated antigens and molecules involved in antigen processing and presentation in three cell lines established from a single patient. Melanoma Res 14:463–471PubMedCrossRef
45.
go back to reference Romani N, Reider D, Heuer M, Ebner S, Kampgen E, Eibl B, Niederwieser D, Schuler G (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196:137–151PubMedCrossRef Romani N, Reider D, Heuer M, Ebner S, Kampgen E, Eibl B, Niederwieser D, Schuler G (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196:137–151PubMedCrossRef
46.
go back to reference Kalinski P, Wieckowski E, Muthuswamy R, de Jong E (2010) Generation of stable Th1/CTL-, Th2-, and Th17-inducing human dendritic cells. Methods Mol Biol 595:117–133PubMedCrossRef Kalinski P, Wieckowski E, Muthuswamy R, de Jong E (2010) Generation of stable Th1/CTL-, Th2-, and Th17-inducing human dendritic cells. Methods Mol Biol 595:117–133PubMedCrossRef
47.
go back to reference Lane P, Burdet C, McConnell F, Lanzavecchia A, Padovan E (1995) CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation. Eur J Immunol 25:1788–1793PubMedCrossRef Lane P, Burdet C, McConnell F, Lanzavecchia A, Padovan E (1995) CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation. Eur J Immunol 25:1788–1793PubMedCrossRef
48.
go back to reference Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P (2009) Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta 1805:53–71PubMed Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P (2009) Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta 1805:53–71PubMed
49.
go back to reference Obeid M, Panaretakis T, Joza N, Tufi R, Tesniere A, van Endert P, Zitvogel L, Kroemer G (2007) Calreticulin exposure is required for the immunogenicity of gamma-irradiation and UVC light-induced apoptosis. Cell Death Differ 14:1848–1850PubMedCrossRef Obeid M, Panaretakis T, Joza N, Tufi R, Tesniere A, van Endert P, Zitvogel L, Kroemer G (2007) Calreticulin exposure is required for the immunogenicity of gamma-irradiation and UVC light-induced apoptosis. Cell Death Differ 14:1848–1850PubMedCrossRef
50.
go back to reference Wieckowski E, Chatta GS, Mailliard RM, Gooding W, Palucka K, Banchereau J, Kalinski P (2010) Type-1 polarized dendritic cells loaded with apoptotic prostate cancer cells are potent inducers of CD8(+) T cells against prostate cancer cells and defined prostate cancer-specific epitopes. Prostate 71:125–133PubMedCrossRef Wieckowski E, Chatta GS, Mailliard RM, Gooding W, Palucka K, Banchereau J, Kalinski P (2010) Type-1 polarized dendritic cells loaded with apoptotic prostate cancer cells are potent inducers of CD8(+) T cells against prostate cancer cells and defined prostate cancer-specific epitopes. Prostate 71:125–133PubMedCrossRef
51.
go back to reference Denoeud J, Moser M (2010) Role of CD27/CD70 pathway of activation in immunity and tolerance. J Leukoc Biol 89:195–203PubMedCrossRef Denoeud J, Moser M (2010) Role of CD27/CD70 pathway of activation in immunity and tolerance. J Leukoc Biol 89:195–203PubMedCrossRef
52.
go back to reference Tamir A, Basagila E, Kagahzian A, Jiao L, Jensen S, Nicholls J, Tate P, Stamp G, Farzaneh F, Harrison P, Stauss H, George AJ, Habib N, Lechler RI, Lombardi G (2007) Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother 56:2003–2016PubMedCrossRef Tamir A, Basagila E, Kagahzian A, Jiao L, Jensen S, Nicholls J, Tate P, Stamp G, Farzaneh F, Harrison P, Stauss H, George AJ, Habib N, Lechler RI, Lombardi G (2007) Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother 56:2003–2016PubMedCrossRef
53.
go back to reference Hatfield P, Merrick AE, West E, O’Donnell D, Selby P, Vile R, Melcher AA (2008) Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J Immunother 31:620–632PubMedCrossRef Hatfield P, Merrick AE, West E, O’Donnell D, Selby P, Vile R, Melcher AA (2008) Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J Immunother 31:620–632PubMedCrossRef
54.
go back to reference Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P (2000) Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J Immunol 164:4507–4512PubMed Vieira PL, de Jong EC, Wierenga EA, Kapsenberg ML, Kalinski P (2000) Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction. J Immunol 164:4507–4512PubMed
55.
go back to reference Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN (2007) Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 82:1365–1374PubMedCrossRef Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN (2007) Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 82:1365–1374PubMedCrossRef
56.
go back to reference Kalinski P, Hilkens CM, Wierenga EA, Kapsenberg ML (1999) T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today 20:561–567PubMedCrossRef Kalinski P, Hilkens CM, Wierenga EA, Kapsenberg ML (1999) T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today 20:561–567PubMedCrossRef
57.
go back to reference Trepiakas R, Pedersen AE, Met O, Hansen MH, Berntsen A, Svane IM (2008) Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients. Vaccine 26:2824–2832PubMedCrossRef Trepiakas R, Pedersen AE, Met O, Hansen MH, Berntsen A, Svane IM (2008) Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients. Vaccine 26:2824–2832PubMedCrossRef
58.
go back to reference Giermasz AS, Urban JA, Nakamura Y, Watchmaker P, Cumberland RL, Gooding W, Kalinski P (2009) Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines. Cancer Immunol Immunother 58:1329–1336PubMedCrossRef Giermasz AS, Urban JA, Nakamura Y, Watchmaker P, Cumberland RL, Gooding W, Kalinski P (2009) Type-1 polarized dendritic cells primed for high IL-12 production show enhanced activity as cancer vaccines. Cancer Immunol Immunother 58:1329–1336PubMedCrossRef
59.
go back to reference Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176:4894–4901PubMed Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176:4894–4901PubMed
60.
go back to reference Salaun B, Lebecque S, Matikainen S, Rimoldi D, Romero P (2007) Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res 13:4565–4574PubMedCrossRef Salaun B, Lebecque S, Matikainen S, Rimoldi D, Romero P (2007) Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res 13:4565–4574PubMedCrossRef
61.
go back to reference Balachandran S, Roberts PC, Kipperman T, Bhalla KN, Compans RW, Archer DR, Barber GN (2000) Alpha/beta interferons potentiate virus-induced apoptosis through activation of the FADD/Caspase-8 death signaling pathway. J Virol 74:1513–1523PubMedCrossRef Balachandran S, Roberts PC, Kipperman T, Bhalla KN, Compans RW, Archer DR, Barber GN (2000) Alpha/beta interferons potentiate virus-induced apoptosis through activation of the FADD/Caspase-8 death signaling pathway. J Virol 74:1513–1523PubMedCrossRef
62.
go back to reference Tissari J, Siren J, Meri S, Julkunen I, Matikainen S (2005) IFN-alpha enhances TLR3-mediated antiviral cytokine expression in human endothelial and epithelial cells by up-regulating TLR3 expression. J Immunol 174:4289–4294PubMed Tissari J, Siren J, Meri S, Julkunen I, Matikainen S (2005) IFN-alpha enhances TLR3-mediated antiviral cytokine expression in human endothelial and epithelial cells by up-regulating TLR3 expression. J Immunol 174:4289–4294PubMed
63.
go back to reference Sato A, Iizuka M, Nakagomi O, Suzuki M, Horie Y, Konno S, Hirasawa F, Sasaki K, Shindo K, Watanabe S (2006) Rotavirus double-stranded RNA induces apoptosis and diminishes wound repair in rat intestinal epithelial cells. J Gastroenterol Hepatol 21:521–530PubMedCrossRef Sato A, Iizuka M, Nakagomi O, Suzuki M, Horie Y, Konno S, Hirasawa F, Sasaki K, Shindo K, Watanabe S (2006) Rotavirus double-stranded RNA induces apoptosis and diminishes wound repair in rat intestinal epithelial cells. J Gastroenterol Hepatol 21:521–530PubMedCrossRef
64.
go back to reference Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S, Hartmann G (2009) Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest 119:2399–2411PubMed Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S, Hartmann G (2009) Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest 119:2399–2411PubMed
65.
go back to reference Smits EL, Ponsaerts P, Van de Velde AL, Van Driessche A, Cools N, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF (2007) Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells. Leukemia 21:1691–1699PubMedCrossRef Smits EL, Ponsaerts P, Van de Velde AL, Van Driessche A, Cools N, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF (2007) Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells. Leukemia 21:1691–1699PubMedCrossRef
66.
go back to reference Cornforth AN, Fowler AW, Carbonell DJ, Dillman RO (2011) Resistance to the proapoptotic effects of interferon-gamma on melanoma cells used in patient-specific dendritic cell immunotherapy is associated with improved overall survival. Cancer Immunol Immunother 60:123–131PubMedCrossRef Cornforth AN, Fowler AW, Carbonell DJ, Dillman RO (2011) Resistance to the proapoptotic effects of interferon-gamma on melanoma cells used in patient-specific dendritic cell immunotherapy is associated with improved overall survival. Cancer Immunol Immunother 60:123–131PubMedCrossRef
67.
go back to reference Chen T, Guo J, Yang M, Zhu X, Cao X (2011) Chemokine-containing exosomes are released from heat-stressed tumor cells via lipid raft-dependent pathway and act as efficient tumor vaccine. J Immunol 186:2219–2228PubMedCrossRef Chen T, Guo J, Yang M, Zhu X, Cao X (2011) Chemokine-containing exosomes are released from heat-stressed tumor cells via lipid raft-dependent pathway and act as efficient tumor vaccine. J Immunol 186:2219–2228PubMedCrossRef
68.
go back to reference Knudsen S, Schardt A, Buhl T, Boeckmann L, Schon MP, Neumann C, Haenssle HA (2010) Enhanced T-cell activation by immature dendritic cells loaded with HSP70-expressing heat-killed melanoma cells. Exp Dermatol 19:108–116PubMedCrossRef Knudsen S, Schardt A, Buhl T, Boeckmann L, Schon MP, Neumann C, Haenssle HA (2010) Enhanced T-cell activation by immature dendritic cells loaded with HSP70-expressing heat-killed melanoma cells. Exp Dermatol 19:108–116PubMedCrossRef
69.
go back to reference Yokota S, Fujii N (2010) Immunomodulatory activity of extracellular heat shock proteins and their autoantibodies. Microbiol Immunol 54:299–307PubMed Yokota S, Fujii N (2010) Immunomodulatory activity of extracellular heat shock proteins and their autoantibodies. Microbiol Immunol 54:299–307PubMed
70.
go back to reference Uze G, Monneron D (2007) IL-28 and IL-29: newcomers to the interferon family. Biochimie 89:729–734PubMedCrossRef Uze G, Monneron D (2007) IL-28 and IL-29: newcomers to the interferon family. Biochimie 89:729–734PubMedCrossRef
71.
go back to reference Blander JM, Medzhitov R (2006) Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 440:808–812PubMedCrossRef Blander JM, Medzhitov R (2006) Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 440:808–812PubMedCrossRef
72.
go back to reference Schulz O, Diebold SS, Chen M, Naslund TI, Nolte MA, Alexopoulou L, Azuma YT, Flavell RA, Liljestrom P, Reis e Sousa C (2005) Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433:887–892PubMedCrossRef Schulz O, Diebold SS, Chen M, Naslund TI, Nolte MA, Alexopoulou L, Azuma YT, Flavell RA, Liljestrom P, Reis e Sousa C (2005) Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 433:887–892PubMedCrossRef
73.
go back to reference Kacani L, Wurm M, Schwentner I, Andrle J, Schennach H, Sprinzl GM (2005) Maturation of dendritic cells in the presence of living, apoptotic and necrotic tumour cells derived from squamous cell carcinoma of head and neck. Oral Oncol 41:17–24PubMedCrossRef Kacani L, Wurm M, Schwentner I, Andrle J, Schennach H, Sprinzl GM (2005) Maturation of dendritic cells in the presence of living, apoptotic and necrotic tumour cells derived from squamous cell carcinoma of head and neck. Oral Oncol 41:17–24PubMedCrossRef
74.
go back to reference Felzmann T, Huttner KG, Breuer SK, Wimmer D, Ressmann G, Wagner D, Paul P, Lehner M, Heitger A, Holter W (2005) Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses. Cancer Immunol Immunother 54:769–780PubMedCrossRef Felzmann T, Huttner KG, Breuer SK, Wimmer D, Ressmann G, Wagner D, Paul P, Lehner M, Heitger A, Holter W (2005) Semi-mature IL-12 secreting dendritic cells present exogenous antigen to trigger cytolytic immune responses. Cancer Immunol Immunother 54:769–780PubMedCrossRef
75.
go back to reference Frick JS, Grunebach F, Autenrieth IB (2010) Immunomodulation by semi-mature dendritic cells: a novel role of Toll-like receptors and interleukin-6. Int J Med Microbiol 300:19–24PubMedCrossRef Frick JS, Grunebach F, Autenrieth IB (2010) Immunomodulation by semi-mature dendritic cells: a novel role of Toll-like receptors and interleukin-6. Int J Med Microbiol 300:19–24PubMedCrossRef
76.
go back to reference Schuler G, Schuler-Thurner B, Steinman RM (2003) The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 15:138–147PubMedCrossRef Schuler G, Schuler-Thurner B, Steinman RM (2003) The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 15:138–147PubMedCrossRef
77.
go back to reference Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206:1589–1602PubMedCrossRef Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206:1589–1602PubMedCrossRef
78.
go back to reference Abdi K, Singh N, Matzinger P (2006) T-cell control of IL-12p75 production. Scand J Immunol 64:83–92PubMedCrossRef Abdi K, Singh N, Matzinger P (2006) T-cell control of IL-12p75 production. Scand J Immunol 64:83–92PubMedCrossRef
79.
go back to reference Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A (2005) Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 6:769–776PubMedCrossRef Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A (2005) Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 6:769–776PubMedCrossRef
81.
go back to reference Jensen SS, Gad M (2010) Differential induction of inflammatory cytokines by dendritic cells treated with novel TLR-agonist and cytokine based cocktails: targeting dendritic cells in autoimmunity. J Inflamm (Lond) 7:37CrossRef Jensen SS, Gad M (2010) Differential induction of inflammatory cytokines by dendritic cells treated with novel TLR-agonist and cytokine based cocktails: targeting dendritic cells in autoimmunity. J Inflamm (Lond) 7:37CrossRef
82.
go back to reference Tirapu I, Lewis A, Kreutz M, McLinden H, Diebold SS (2008) Freeze-and-thaw-disrupted tumour cells impair the responsiveness of DC to TLR stimulation. Eur J Immunol 38:2740–2750PubMedCrossRef Tirapu I, Lewis A, Kreutz M, McLinden H, Diebold SS (2008) Freeze-and-thaw-disrupted tumour cells impair the responsiveness of DC to TLR stimulation. Eur J Immunol 38:2740–2750PubMedCrossRef
Metadata
Title
Poly(I:C)-induced tumour cell death leads to DC maturation and Th1 activation
Publication date
01-11-2011
Published in
Cancer Immunology, Immunotherapy / Issue 11/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-1058-7
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
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