| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Malaghan Institute of Medical Research, Wellington, New Zealand
Dendritic cell (DC)-based vaccination represents a promising approach to harness the specificity and potency of the immune system to combat cancer. Finding optimal strategies for tumor Ag preparation and subsequent pulsing of DC, as well as improving the immunogenicity of weak tumor Ags remain among the first challenges of this approach. In this report, we use a prophylactic vaccine consisting of DC loaded with whole, nonmanipulated B16-F10 melanoma cells that had been stressed by heat shock and gamma irradiation. Stressed B16-F10 cells underwent apoptosis and were internalized by bone marrow-derived DC during coculture. Surprisingly, coculture of DC with stressed B16-F10 undergoing apoptosis and necrosis did not induce DC maturation. However, a marked retardation in tumor growth was observed in C57BL/6 mice immunized using DC loaded with stressed B16-F10 cells and subsequently challenged with B16-F10 cells. Growth retardation was further increased by treating DC with LPS before in vivo administration. In vivo depletion studies revealed that both CD8+ and CD4+ T cells played a critical role in retarding tumor growth. In addition, treatment with anti-CD25 Ab to deplete CD4+CD25+ regulatory T cells before DC vaccination considerably improved the effect of the vaccine and allowed the development of long-lived immune responses that were tumor protective. Our results demonstrate that depletion of regulatory T cells is an effective approach to improving the success of DC-based vaccination against weakly immunogenic tumors. Such a strategy can be readily applied to other tumor models and extended to therapeutic vaccination settings.
This article has been cited by other articles:
|
|
 |
|
  A. P. Castano, P. Mroz, M. X. Wu, and M. R. Hamblin Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model PNAS, April 8, 2008; 105(14): 5495 - 5500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Larmonier, J. Cantrell, C. LaCasse, G. Li, N. Janikashvili, E. Situ, M. Sepassi, S. Andreansky, and E. Katsanis Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression J. Leukoc. Biol., April 1, 2008; 83(4): 1049 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Cools, P. Ponsaerts, V. F. I. Van Tendeloo, and Z. N. Berneman Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells J. Leukoc. Biol., December 1, 2007; 82(6): 1365 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Elpek, C. Lacelle, N. P. Singh, E. S. Yolcu, and H. Shirwan CD4+CD25+ T Regulatory Cells Dominate Multiple Immune Evasion Mechanisms in Early but Not Late Phases of Tumor Development in a B Cell Lymphoma Model J. Immunol., June 1, 2007; 178(11): 6840 - 6848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Banerjee, M. V. Dhodapkar, E. Matayeva, R. M. Steinman, and K. M. Dhodapkar Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients Blood, October 15, 2006; 108(8): 2655 - 2661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vojdani and J. Erde Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: Modulating Tumor Immunity, Autoimmunity and Alloreactive Immunity (III) Evid. Based Complement. Altern. Med., September 1, 2006; 3(3): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Beyer and J. L. Schultze Regulatory T cells in cancer Blood, August 1, 2006; 108(3): 804 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Valzasina, S. Piconese, C. Guiducci, and M. P. Colombo Tumor-Induced Expansion of Regulatory T Cells by Conversion of CD4+CD25- Lymphocytes Is Thymus and Proliferation Independent. Cancer Res., April 15, 2006; 66(8): 4488 - 4495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lizee, L. G. Radvanyi, W. W. Overwijk, and P. Hwu Immunosuppression in melanoma immunotherapy: potential opportunities for intervention. Clin. Cancer Res., April 1, 2006; 12(7): 2359s - 2365s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, S. P. Huck, R. S. McHugh, I. F. Hermans, and F. Ronchese Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo PNAS, January 3, 2006; 103(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wolf, A. M. Wolf, H. Rumpold, H. Fiegl, A. G. Zeimet, E. Muller-Holzner, M. Deibl, G. Gastl, E. Gunsilius, and C. Marth The Expression of the Regulatory T Cell-Specific Forkhead Box Transcription Factor FoxP3 Is Associated with Poor Prognosis in Ovarian Cancer Clin. Cancer Res., December 1, 2005; 11(23): 8326 - 8331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Hokey, A. T. Larregina, G. Erdos, S. C. Watkins, and L. D. Falo Jr. Tumor Cell Loaded Type-1 Polarized Dendritic Cells Induce Th1-Mediated Tumor Immunity Cancer Res., November 1, 2005; 65(21): 10059 - 10067. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
