| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
1 Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, Florida, and
2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
A better understanding of how solid malignancies arise in an immunocompetent host, avoid immune recognition, and ultimately progress to widely disseminated cancer is essential to effectively harness the immune system against solid tumors. Because of their extra-lymphatic localization, it has been proposed that solid malignancies are just ignored by the immune system, thereby allowing their uncontrolled growth and dissemination. Alternatively, as most of the solid tumors are unable to express costimulatory molecules, the "signal one without signal two" model of tolerance induction has been frequently evoked to account for the failure of the immune system to reject antigenic tumors in vivo. In this study, we showed, however, that the extra-lymphatic growth of solid tumors is not immunologically ignored by the lymphoid compartment, resulting instead in the early induction of antigen-specific CD4+ T-cell tolerance. Furthermore, analysis of parent-into-F1 bone marrow (BM) chimeras demonstrates that presentation of tumor antigens by BM-derived antigen-presenting cells represents the dominant mechanism in solid tumor-induced CD4+ T-cell tolerance. Our findings of early development of antigen-specific T-cell unresponsiveness mediated by BM-derived antigen-presenting cells, not only provides a plausible explanation for the failure of the immune system to reject antigenic solid tumors in vivo, but more importantly, they have identified a barrier that, if appropriately manipulated, may lead to approaches to effectively harness the immune system against solid malignancies.
This article has been cited by other articles:
|
|
 |
|
  Z.-Z. Yang, A. J. Novak, S. C. Ziesmer, T. E. Witzig, and S. M. Ansell CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25 T cells Blood, October 1, 2007; 110(7): 2537 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Morimoto, X. Tan, R. M. Teague, C. Ohlen, and P. D. Greenberg Induction of Tolerance in CD8+ T Cells to a Transgenic Autoantigen Expressed in the Liver Does Not Require Cross-Presentation J. Immunol., June 1, 2007; 178(11): 6849 - 6860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhou and H. I. Levitsky Natural Regulatory T Cells and De Novo-Induced Regulatory T Cells Contribute Independently to Tumor-Specific Tolerance J. Immunol., February 15, 2007; 178(4): 2155 - 2162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Brown, C. Blank, J. Kline, A. K. Kacha, and T. F. Gajewski Homeostatic Proliferation as an Isolated Variable Reverses CD8+ T Cell Anergy and Promotes Tumor Rejection J. Immunol., October 1, 2006; 177(7): 4521 - 4529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Joncker, J. Helft, A. Jacquet, V. Premel, and O. Lantz Intratumor CD4 T-cell accumulation requires stronger priming than for expansion and lymphokine secretion. Cancer Res., May 15, 2006; 66(10): 5443 - 5451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Overwijk, K. E. de Visser, F. H. Tirion, L. A. de Jong, T. W. H. Pols, Y. U. van der Velden, J. G. van den Boorn, A. M. Keller, W. A. Buurman, M. R. Theoret, et al. Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant J. Immunol., May 1, 2006; 176(9): 5213 - 5222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Huang, P.-Y. Pan, Q. Li, A. I. Sato, D. E. Levy, J. Bromberg, C. M. Divino, and S.-H. Chen Gr-1+CD115+ Immature Myeloid Suppressor Cells Mediate the Development of Tumor-Induced T Regulatory Cells and T-Cell Anergy in Tumor-Bearing Host Cancer Res., January 15, 2006; 66(2): 1123 - 1131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhou, C. G. Drake, and H. I. Levitsky Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines Blood, January 15, 2006; 107(2): 628 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kusmartsev, S. Nagaraj, and D. I. Gabrilovich Tumor-Associated CD8+ T Cell Tolerance Induced by Bone Marrow-Derived Immature Myeloid Cells J. Immunol., October 1, 2005; 175(7): 4583 - 4592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Liu, S. A. Caldwell, and S. I. Abrams Immune Selection and Emergence of Aggressive Tumor Variants as Negative Consequences of Fas-Mediated Cytotoxicity and Altered IFN-{gamma}-Regulated Gene Expression Cancer Res., May 15, 2005; 65(10): 4376 - 4388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Demaria, F. R. Santori, B. Ng, L. Liebes, S. C. Formenti, and S. Vukmanovic Select forms of tumor cell apoptosis induce dendritic cell maturation J. Leukoc. Biol., March 1, 2005; 77(3): 361 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, F. Cheng, A. Cuenca, P. Horna, Z. Zheng, K. Bhalla, and E. M. Sotomayor Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance Blood, February 1, 2005; 105(3): 1135 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zhou, Z. Lu, J. D. McCadden, H. I. Levitsky, and A. L. Marson Reciprocal Changes in Tumor Antigenicity and Antigen-specific T Cell Function during Tumor Progression J. Exp. Med., December 20, 2004; 200(12): 1581 - 1592. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
