Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Seminars in Immunopathology
Published in: Seminars in Immunopathology 3/2005

01-01-2005 | Original Article

Modulation of antitumor responses by dendritic cells

Authors: Johannes Vieweg, Andrew Jackson

Published in: Seminars in Immunopathology | Issue 3/2005

Login to get access

Abstract

The discovery that dendritic cells (DC) play a key role in regulating antitumor immunity has prompted considerable efforts in developing DC-based cancer vaccines for use in clinical oncology. Early translational trials using antigen-loaded DC have established clear evidence of vaccine safety, and demonstrated bioactivity by stimulating immunological and even clinical responses in selected subjects. Despite these encouraging results, the vaccine-induced immune responses achieved to date are not yet sufficient to attain a robust and durable therapeutic effect in the cancer patient. Therefore, further improvements are required to enhance vaccine potency and optimize the potential for clinical success. This article presents a set of emerging concepts that, together, form a framework for a multi-pronged approach that will further enhance the efficacy of DC-based vaccination by either directly improving DC-mediated T cell activation or by inhibiting mechanisms that suppress the induction of an effective antitumor response. The clinical translation of these concepts will result in new opportunities to successfully modulate immune responses in clinical settings.
Literature
1.
Alexandroff AB, Jackson AM, O’Donnell MA, et al (1999) BCG immunotherapy of bladder cancer: 20 years on. Lancet 353:1689
2.
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245
3.
Bhardwaj N (2001) Processing and presentation of antigens by dendritic cells: implications for vaccines. Trends Mol Med 7:388
4.
Bronte V, Serafini P, De Santo C, et al (2003) IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J Immunol 170:270
5.
Carson-Walter EB, Watkins DN, Nanda A, et al (2001) Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res 61:6649
6.
Chakraborty M, Abrams SI, Coleman CN, et al (2004) External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res 64:4328
7.
Coggin JH Jr, Barsoum AL, Rohrer JW (1998) Tumors express both unique TSTA and crossprotective 44 kDa oncofetal antigen. Immunol Today 19:405
8.
Cranmer LD, Trevor KT, Hersh EM (2004) Clinical applications of dendritic cell vaccination in the treatment of cancer. Cancer Immunol Immunother 53:275
9.
Dhodapkar MV, Steinman RM, Krasovsky J, et al (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233
10.
Fong GH, Rossant J, Gertsenstein M, et al (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66
11.
Fong L, Engleman EG (2000) Dendritic cells in cancer immunotherapy. Annu Rev Immunol 18:245
12.
Gramaglia I, Cooper D, Miner KT, et al (2000) Co-stimulation of antigen-specific CD4 T cells by 4-1BB ligand. Eur J Immunol 30:392
13.
Greenberg PD, Kern DE, Cheever MA (1985) Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+,2− T cells. Tumor eradication does not require participation of cytotoxic T cells. J Exp Med 161:1122
14.
Hung K, Hayashi R, Lafond-Walker A, et al (1998) The central role of CD4(+) T cells in the antitumor immune response. J Exp Med 188:2357
15.
Jonuleit H, Kuhn U, Muller G, et al (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur J Immunol 27:3135
16.
Kalams SA, Walker BD (1998) The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses. J Exp Med 188:2199
17.
Kalinski P, Hilkens CM, Wierenga EA, et al (1999) T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today 20:561
18.
Keilholz U, Weber J, Finke JH, et al (2002) Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the society for biological therapy. J Immunother 25:97
19.
Kjaergaard J, Tanaka J, Kim JA, et al (2000) Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res 60:5514
20.
Krieg AM (1999) Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides. Biochim Biophys Acta 1489:107
21.
Kusmartsev S, Cheng F, Yu B, et al (2003) All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 63:4441
22.
Kusmartsev S, Nefedova Y, Yoder D, et al (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989
23.
Laderach D, Compagno D, Danos O, et al (2003) RNA interference shows critical requirement for NF-kappa B p50 in the production of IL-12 by human dendritic cells. J Immunol 171:1750
24.
Lane P (2000) Role of OX40 signals in coordinating CD4 T cell selection, migration, and cytokine differentiation in T helper (Th)1 and Th2 cells. J Exp Med 191:201
25.
Langenkamp A, Messi M, Lanzavecchia A, et al (2000) Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol 1:311
26.
Li Y, Wang MN, Li H, et al (2002) Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med 195:1575
27.
Lin KY, Guarnieri FG, Staveley-O’Carroll KF, et al (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 56:21
28.
Luft T, Jefford M, Luetjens P, et al (2002) Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E regulates the migratory capacity of specific DC subsets. Blood 100:1362
29.
Martin E, O’Sullivan B, Low P, et al (2003) Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 18:155
30.
MartIn-Fontecha A, Sebastiani S, Hopken UE, et al (2003) Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 198:615
31.
Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991
32.
Maxwell JR, Weinberg A, Prell RA, et al (2000) Danger and OX40 receptor signaling synergize to enhance memory T cell survival by inhibiting peripheral deletion. J Immunol 164:107
33.
Melief CJ, Toes, RE, Medema, JP, et al (2000) Strategies for immunotherapy of cancer. Adv Immunol 75:235
34.
Menges M, Rossner S, Voigtlander C, et al (2002) Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. J Exp Med 195:15
35.
Morse MA, Lyerly HK, Gilboa E, et al (1998) Optimization of the sequence of antigen loading and CD40-ligand-induced maturation of dendritic cells. Cancer Res 58:2965
36.
Mumberg D, Monach PA, Wanderling S, et al (1999) CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc Natl Acad Sci USA 96:8633
37.
Nair S, Boczkowski D, Moeller B, et al (2003) Synergy between tumor immunotherapy and antiangiogenic therapy. Blood 102:964
38.
Nair S, McLaughlin C, Weizer A, et al (2003) Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation. J Immunol 171:6275
39.
Nair SK, Heiser A, Boczkowski D, et al (2000) Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. Nat Med 6:1011
40.
Nelson AR, Fingleton B, Rothenberg ML, et al (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135
41.
Niethammer AG, Xiang R, Becker JC, et al (2002) A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 8:1369
42.
Ohshima Y, Tanaka Y, Tozawa H, et al (1997) Expression and function of OX40 ligand on human dendritic cells. J Immunol 159:3838
43.
Olsen E, Duvic M, Frankel A, et al (2001) Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol 19:376
44.
Onizuka S, Tawara I, Shimizu J, et al (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59:3128
45.
Pardoll DM, Topalian SL (1998) The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol 10:588
46.
Phan GQ, Yang JC, Sherry RM, et al (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 100:8372
47.
Pulendran B, Palucka K, Banchereau J (2001) Sensing pathogens and tuning immune responses. Science 293:253
48.
Qazilbash MH, Giralt SA, Champlin RE (2004) Nonmyeloablative stem cell transplantation for chronic myeloid leukemia. Hematol Oncol Clin North Am 18:703
49.
Qin Z, Blankenstein T (2000) CD4+ T cell-mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells. Immunity 12:677
50.
Ridge JP, Di Rosa F, Matzinger P (1998) A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393:474
51.
Romani N, Reider D, Heuer M, et al (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196:137
52.
Rosenberg SA (1999) A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 10:281
53.
Ruedl C, Bachmann MF, Kopf M (2000) The antigen dose determines T helper subset development by regulation of CD40 ligand. Eur J Immunol 30:2056
54.
Santulli-Marotto S, Nair SK, Rusconi C, et al (2003) Multivalent RNA aptamers that inhibit CTLA-4 and enhance tumor immunity. Cancer Res 63:7483
55.
Schuler-Thurner B, Schultz ES, Berger TG, et al (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
56.
Seder RA, Ahmed R (2003) Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 4:835
57.
Serafini P, De Santo C, Marigo I, et al (2004) Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 53:64
58.
Shevach EM (2001) Certified professionals: CD4(+)CD25(+) suppressor T cells. J Exp Med 193:F41
59.
Shevach EM, McHugh RS, Piccirillo CA, et al (2001) Control of T-cell activation by CD4+ CD25+ suppressor T cells. Immunol Rev 182:58
60.
Shimizu J, Yamazaki S, Sakaguchi S (1999) Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 163:5211
61.
Siegel S, Wagner A, Schmitz N, et al (2003) Induction of antitumour immunity using survivin peptide-pulsed dendritic cells in a murine lymphoma model. Br J Haematol 122:911
62.
Smith JW 2nd, Walker EB, Fox BA, et al (2003) Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. J Clin Oncol 21:1562
63.
Steinbrink K, Wolfl M, Jonuleit H, et al (1997) Induction of tolerance by IL-10-treated dendritic cells. J Immunol 159:4772
64.
Su JM, Wei YQ, Tian L, et al (2003) Active immunogene therapy of cancer with vaccine on the basis of chicken homologous matrix metalloproteinase-2. Cancer Res 63:600
65.
Su Z, Vieweg J, Weizer A, et al (2002) Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product. Cancer Res 62:5041
66.
Sutmuller RP, Duivenvoorde LM van, Elsas A van, et al (2001) Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 194:823
67.
Suzuki H, Wang B, Shivji GM, et al (2000) Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J Invest Dermatol 114:135
68.
Svane IM, Pedersen AE, Johnsen HE, et al (2004) Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother 53:633
69.
Testerman TL, Gerster JF, Imbertson LM, et al (1995) Cytokine induction by the immunomodulators imiquimod and S-27609. J Leukoc Biol 58:365
70.
Vonderheide RH, Domchek SM, Schultze JL, et al (2004) Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin Cancer Res 10:828
71.
Vonderheide RH, Hahn WC, Schultze JL, et al (1999) The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 10:673
72.
Wang T, Niu G, Kortylewski M, et al (2004) Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 10:48
73.
Weeks CE, Gibson SJ (1994) Induction of interferon and other cytokines by imiquimod and its hydroxylated metabolite R-842 in human blood cells in vitro. J Interferon Res 14:81
74.
Wei YQ, Wang QR, Zhao X, et al (2000) Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine. Nat Med 6:1160
75.
Weinberg AD, Rivera MM, Prell R, et al (2000) Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 164:2160
76.
Wherry EJ, Teichgraber V, Becker TC, et al (2003) Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 4:225
77.
Wu T-C, Guarnier FG, Staveley-O’Carroll KF, et al (1995) Engineering an intracellular pathyway for major histocompatibility complex class II presentation of antigens. Proc Natl Acad Sci USA 92:11671
78.
Yu P, Spiotto MT, Lee Y, et al (2003) Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigen to CD8+ T cells. J Exp Med 197:985
79.
Zeis M, Siegel S, Wagner A, et al (2003) Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells. J Immunol 170:5391
Metadata
Title
Modulation of antitumor responses by dendritic cells
Authors
Johannes Vieweg
Andrew Jackson
Publication date
01-01-2005
Publisher
Springer-Verlag
Published in
Seminars in Immunopathology / Issue 3/2005
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-004-0175-1

Other articles of this Issue 3/2005

Seminars in Immunopathology 3/2005 Go to the issue

Original Article

Dendritic cell chic

Original Article

Induction of antigen cross-presentation by Toll-like receptors

Original Article

Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9

Original Paper

Dendritic cell-mediated T cell polarization

Original Article

Pathways for antigen cross presentation

Original Paper

Factors and signals that govern the migration of dendritic cells via lymphatics: recent advances
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits