Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2011, Vol. 5 Issue (4) : 323-332     DOI: 10.1007/s11684-011-0172-4
Dendritic cell vaccines in cancer immunotherapy: from biology to translational medicine
Hongmei Xu(), Xuetao Cao
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China
Download: PDF(209 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Corresponding Authors: Xu Hongmei,   
Issue Date: 05 December 2011
URL:     OR
Fig.1  Monocyte-derived DCs cultured in the presence of GM-CSF and IL-4. (A) Immature DCs; (B) Mature DCs
1 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69–90
doi: 10.3322/caac.20107 pmid:21296855
2 Lesterhuis WJ, Haanen JB, Punt CJ. Cancer immunotherapy—revisited. Nat Rev Drug Discov 2011; 10(8): 591–600
doi: 10.1038/nrd3500 pmid:21804596
3 Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973; 137(5): 1142–1162
doi: 10.1084/jem.137.5.1142 pmid:4573839
4 Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 1992; 176(6): 1693–1702
doi: 10.1084/jem.176.6.1693 pmid:1460426
5 Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2(1): 52–58
doi: 10.1038/nm0196-52 pmid:8564842
6 Steinman RM, Mellman I. Immunotherapy: bewitched, bothered, and bewildered no more. Science 2004; 305(5681): 197–200
doi: 10.1126/science.1099688 pmid:15247468
7 Schadendorf D, Ugurel S, Schuler-Thurner B, Nestle FO, Enk A, Br?cker EB, Grabbe S, Rittgen W, Edler L, Sucker A, Zimpfer-Rechner C, Berger T, Kamarashev J, Burg G, Jonuleit H, Tüttenberg A, Becker JC, Keikavoussi P, K?mpgen E, Schuler G; DCs study group of the DeCOG. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed DCs (DCs) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DCs study group of the DeCOG. Ann Oncol 2006; 17(4): 563–570
doi: 10.1093/annonc/mdj138 pmid:16418308
9 Miller MJ, Safrina O, Parker I, Cahalan MD. Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J Exp Med 2004; 200(7): 847–856
doi: 10.1084/jem.20041236 pmid:15466619
10 Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol 2005; 5(8): 617–628
doi: 10.1038/nri1670 pmid:16056255
11 Heath WR, Belz GT, Behrens GM, Smith CM, Forehan SP, Parish IA, Davey GM, Wilson NS, Carbone FR, Villadangos JA. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 2004; 199(1): 9–26
doi: 10.1111/j.0105-2896.2004.00142.x pmid:15233723
12 Xu S, Han Y, Xu X, Bao Y, Zhang M, Cao X. IL-17A-producing γδT cells promote CTL responses against Listeria monocytogenes infection by enhancing dendritic cell cross-presentation. J Immunol 2010; 185(10): 5879–5887
doi: 10.4049/jimmunol.1001763 pmid:20956351
13 Cranmer LD, Trevor KT, Hersh EM. Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother 2004; 53(4): 275–306
doi: 10.1007/s00262-003-0432-5 pmid:14648069
14 Schuler G, Schuler-Thurner B, Steinman RM. The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 2003; 15(2): 138–147
doi: 10.1016/S0952-7915(03)00015-3 pmid:12633662
15 Romani N, Gruner S, Brang D, K?mpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med 1994; 180(1): 83–93
doi: 10.1084/jem.180.1.83 pmid:8006603
16 Jonuleit H, Kühn U, Müller G, Steinbrink K, Paragnik L, Schmitt E, Knop J, Enk AH. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 1997; 27(12): 3135–3142
doi: 10.1002/eji.1830271209 pmid:9464798
17 Luft T, Jefford M, Luetjens P, Toy T, Hochrein H, Masterman KA, Maliszewski C, Shortman K, Cebon J, Maraskovsky E. Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E(2) regulates the migratory capacity of specific DC subsets. Blood 2002; 100(4): 1362–1372
doi: 10.1182/blood-2001-12-0360 pmid:12149219
18 Morelli AE, Thomson AW. Dendritic cells under the spell of prostaglandins. Trends Immunol 2003; 24(3): 108–111
doi: 10.1016/S1471-4906(03)00023-1 pmid:12615202
19 Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, Cannistra S, Avigan D, Kufe D. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 2000; 165(3): 1705–1711
20 Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 2005; 5(4): 296–306
doi: 10.1038/nri1592 pmid:15803149
21 Gilboa E, Vieweg J. Cancer immunotherapy with mRNA-transfected dendritic cells. Immunol Rev 2004; 199(1): 251–263
doi: 10.1111/j.0105-2896.2004.00139.x pmid:15233739
22 Wang Q, Liu Y, Wang J, Ding G, Zhang W, Chen G, Zhang M, Zheng S, Cao X. Induction of allospecific tolerance by immature dendritic cells genetically modified to express soluble TNF receptor. J Immunol 2006; 177(4): 2175–2185
23 Breckpot K, Aerts JL, Thielemans K. Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics. Gene Ther 2007; 14(11): 847–862
doi: 10.1038/ pmid:17361214
24 Gilboa E. DC-based cancer vaccines. J Clin Invest 2007; 117(5): 1195–1203
doi: 10.1172/JCI31205 pmid:17476349
25 Shi L, Luo K, Xia D, Chen T, Chen G, Jiang Y, Li N, Cao X. DIgR2, dendritic cell-derived immunoglobulin receptor 2, is one representative of a family of IgSF inhibitory receptors and mediates negative regulation of dendritic cell-initiated antigen-specific T-cell responses. Blood 2006; 108(8): 2678–2686
doi: 10.1182/blood-2006-04-015404 pmid:16794255
26 Adema GJ, de Vries IJ, Punt CJ, Figdor CG. Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol 2005; 17(2): 170–174
doi: 10.1016/j.coi.2005.01.004 pmid:15766677
27 Eggert AA, Schreurs MW, Boerman OC, Oyen WJ, de Boer AJ, Punt CJ, Figdor CG, Adema GJ. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 1999; 59(14): 3340–3345
28 De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, Adema GJ, Punt CJ, Figdor CG. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 2003; 63(1): 12–17
29 Martin-Fontecha A, Sebastiani S, H?pken UE, Uguccioni M, Lipp M, Lanzavecchia A, Sallusto F. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 2003; 198(4): 615–621
doi: 10.1084/jem.20030448 pmid:12925677
30 Nair S, McLaughlin C, Weizer A, Su Z, Boczkowski D, Dannull J, Vieweg J, Gilboa E. Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation. J Immunol 2003; 171(11): 6275–6282
31 Wan T, Zhou X, Chen G, An H, Chen T, Zhang W, Liu S, Jiang Y, Yang F, Wu Y, Cao X. Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant. Blood 2004; 103(5): 1747–1754
doi: 10.1182/blood-2003-08-2828 pmid:14592822
32 Wu Y, Wan T, Zhou X, Wang B, Yang F, Li N, Chen G, Dai S, Liu S, Zhang M, Cao X. Hsp70-like protein 1 fusion protein enhances induction of carcinoembryonic antigen-specific CD8+ CTL response by dendritic cell vaccine. Cancer Res 2005; 65(11): 4947–4954
doi: 10.1158/0008-5472.CAN-04-3912 pmid:15930317
33 Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 2002; 196(12): 1627–1638
doi: 10.1084/jem.20021598 pmid:12486105
34 Tacken PJ, de Vries IJ, Torensma R, Figdor CG. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 2007; 7(10): 790–802
doi: 10.1038/nri2173 pmid:17853902
35 Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9(3): 162–174
doi: 10.1038/nri2506 pmid:19197294
36 Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006; 6(4): 295–307
doi: 10.1038/nri1806 pmid:16557261
37 Liu Q, Zhang C, Sun A, Zheng Y, Wang L, Cao X. Tumor-educated CD11bhighIalow regulatory dendritic cells suppress T cell response through arginase I. J Immunol 2009; 182(10): 6207–6216
doi: 10.4049/jimmunol.0803926 pmid:19414774
38 Lake RA, Robinson BW. Immunotherapy and chemotherapy—a practical partnership. Nat Rev Cancer 2005; 5(5): 397–405
doi: 10.1038/nrc1613 pmid:15864281
39 Restifo NP. Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity. Curr Opin Immunol 2000; 12(5): 597–603
doi: 10.1016/S0952-7915(00)00148-5 pmid:11007365
40 Chen T, Cao X. Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunity. Eur J Immunol 2010; 40(6): 1541–1544
doi: 10.1002/eji.201040616 pmid:20468008
41 Spisek R, Charalambous A, Mazumder A, Vesole DH, Jagannath S, Dhodapkar MV. 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 2007; 109(11): 4839–4845
doi: 10.1182/blood-2006-10-054221 pmid:17299090
42 Chen T, Guo J, Han C, Yang M, Cao X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J Immunol 2009; 182(3): 1449–1459
43 Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, André F, Delaloge S, Tursz T, Kroemer G, Zitvogel L. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 2007; 13(9): 1050–1059
doi: 10.1038/nm1622 pmid:17704786
44 Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 2006; 12(4): 1260–1269
doi: 10.1158/1078-0432.CCR-05-2059 pmid:16489082
45 Small EJ, Fratesi P, Reese DM, Strang G, Laus R, Peshwa MV, Valone FH. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 2000; 18(23): 3894–3903
46 Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators.Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363(5): 411–422
doi: 10.1056/NEJMoa1001294 pmid:20818862
47 Burch PA, Breen JK, Buckner JC, Gastineau DA, Kaur JA, Laus RL, Padley DJ, Peshwa MV, Pitot HC, Richardson RL, Smits BJ, Sopapan P, Strang G, Valone FH, Vuk-Pavlovi? S. Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clin Cancer Res 2000; 6(6): 2175–2182
48 Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006; 24(19): 3089–3094
doi: 10.1200/JCO.2005.04.5252 pmid:16809734
49 Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res 2011; 17(11): 3520–3526
doi: 10.1158/1078-0432.CCR-10-3126 pmid:21471425
51 Scholer A, Hugues S, Boissonnas A, Fetler L, Amigorena S. Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory. Immunity 2008; 28(2): 258–270
doi: 10.1016/j.immuni.2007.12.016 pmid:18275834
52 Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 2009; 115(16): 3670–3679
doi: 10.1002/cncr.24429 pmid:19536890
53 DeFrancesco L. Landmark approval for Dendreon’s cancer vaccine. Nat Biotechnol 2010; 28(6): 531–532
doi: 10.1038/nbt0610-531 pmid:20531312
54 Janetzki S, Britten CM, Kalos M, Levitsky HI, Maecker HT, Melief CJ, Old LJ, Romero P, Hoos A, Davis MM. “MIATA”-minimal information about T cell assays. Immunity 2009; 31(4): 527–528
doi: 10.1016/j.immuni.2009.09.007 pmid:19833080
55 Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, H?kansson L, Janetzki S, Kawakami Y, Kleen TO, Lee PP, Maccalli C, Maecker HT, Maino VC, Maio M, Malyguine A, Masucci G, Pawelec G, Potter DM, Rivoltini L, Salazar LG, Schendel DJ, Slingluff CL Jr, Song W, Stroncek DF, Tahara H, Thurin M, Trinchieri G, van Der Burg SH, Whiteside TL, Wigginton JM, Marincola F, Khleif S, Fox BA, Disis ML. Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers. Clin Cancer Res 2011; 17(10): 3064–3076
doi: 10.1158/1078-0432.CCR-10-2234 pmid:21558394
56 Butterfield LH, Gooding W, Whiteside TL. Development of a potency assay for human dendritic cells: IL-12p70 production. J Immunother 2008; 31(1): 89–100
doi: 10.1097/CJI.0b013e318158fce0 pmid:18157016
57 Weber J. Ipilimumab: controversies in its development, utility and autoimmune adverse events. Cancer Immunol Immunother 2009; 58(5): 823–830
doi: 10.1007/s00262-008-0653-8 pmid:19198837
58 Hoos A, Parmiani G, Hege K, Sznol M, Loibner H, Eggermont A, Urba W, Blumenstein B, Sacks N, Keilholz U, Nichol G. A clinical development paradigm for cancer vaccines and related biologics. J Immunother 2007; 30(1): 1–15
doi: 10.1097/ pmid:17198079
59 Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228–247
doi: 10.1016/j.ejca.2008.10.026 pmid:19097774
60 Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15(23): 7412–7420
doi: 10.1158/1078-0432.CCR-09-1624 pmid:19934295
61 Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, Humphrey R, Blumenstein B, Old L, Wolchok J. Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 2010; 102(18): 1388–1397
doi: 10.1093/jnci/djq310 pmid:20826737
62 U.S. Food and Drug Administration. Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics, April2005.
63 Draube A, Klein-González N, Mattheus S, Brillant C, Hellmich M, Engert A, von Bergwelt-Baildon M. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS ONE 2011; 6(4): e18801
doi: 10.1371/journal.pone.0018801 pmid:21533099
64 Dougan M, Dranoff G. Immune therapy for cancer. Annu Rev Immunol 2009; 27(1): 83–117
doi: 10.1146/annurev.immunol.021908.132544 pmid:19007331
No related articles found!
Full text