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Cutting Edge |




* Abramson Family Cancer Research Institute and Departments of
Surgery and
Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, PA 19104
Active suppression by T regulatory cells plays an important role in the down-regulation of T cell responses to foreign and self-Ags. Thus far, the potential role of CD4+CD25+ T cells in human tumors has not been reported. In this work we show that lung tumors contain large numbers of these cells and that they have constitutive high-level expression of CD152 (CTLA-4). Furthermore, the CD4+CD25+ T cells mediate potent inhibition of autologous T cell proliferation. Finally, regulatory T cells from patient tumors failed to inhibit the proliferation of allogeneic T cells. Together these results suggest that the CD4+CD25+ T cells found in lung tumors selectively inhibit the host immune response and therefore could contribute to the progression of lung cancer.
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L. E. Raez, P. A. Cassileth, J. J. Schlesselman, K. Sridhar, S. Padmanabhan, E. Z. Fisher, P. A. Baldie, and E. R. Podack Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., July 15, 2004; 22(14): 2800 - 2807. [Abstract] [Full Text] [PDF] |
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M. Viguier, F. Lemaitre, O. Verola, M.-S. Cho, G. Gorochov, L. Dubertret, H. Bachelez, P. Kourilsky, and L. Ferradini Foxp3 Expressing CD4+CD25high Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells J. Immunol., July 15, 2004; 173(2): 1444 - 1453. [Abstract] [Full Text] [PDF] |
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J. N. Blattman and P. D. Greenberg Cancer Immunotherapy: A Treatment for the Masses Science, July 9, 2004; 305(5681): 200 - 205. [Abstract] [Full Text] [PDF] |
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Y. Sasaki, M. Sakai, S. Miyazaki, S. Higuma, A. Shiozaki, and S. Saito Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases Mol. Hum. Reprod., May 1, 2004; 10(5): 347 - 353. [Abstract] [Full Text] [PDF] |
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M. Y. Mapara and M. Sykes Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance J. Clin. Oncol., March 15, 2004; 22(6): 1136 - 1151. [Abstract] [Full Text] [PDF] |
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E. M. Aandahl, J. Michaelsson, W. J. Moretto, F. M. Hecht, and D. F. Nixon Human CD4+ CD25+ Regulatory T Cells Control T-Cell Responses to Human Immunodeficiency Virus and Cytomegalovirus Antigens J. Virol., March 1, 2004; 78(5): 2454 - 2459. [Abstract] [Full Text] [PDF] |
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J. Huehn, K. Siegmund, J. C.U. Lehmann, C. Siewert, U. Haubold, M. Feuerer, G. F. Debes, J. Lauber, O. Frey, G. K. Przybylski, et al. Developmental Stage, Phenotype, and Migration Distinguish Naive- and Effector/Memory-like CD4+ Regulatory T Cells J. Exp. Med., February 2, 2004; 199(3): 303 - 313. [Abstract] [Full Text] [PDF] |
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W. Chen, W. Jin, N. Hardegen, K.-j. Lei, L. Li, N. Marinos, G. McGrady, and S. M. Wahl Conversion of Peripheral CD4+CD25- Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-{beta} Induction of Transcription Factor Foxp3 J. Exp. Med., December 15, 2003; 198(12): 1875 - 1886. [Abstract] [Full Text] [PDF] |
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J. Li, P. Hu, L. A. Khawli, and A. L. Epstein Complete Regression of Experimental Solid Tumors by Combination LEC/chTNT-3 Immunotherapy and CD25+ T-Cell Depletion Cancer Res., December 1, 2003; 63(23): 8384 - 8392. [Abstract] [Full Text] [PDF] |
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A. Cavani, F. Nasorri, C. Ottaviani, S. Sebastiani, O. De Pita, and G. Girolomoni Human CD25+ Regulatory T Cells Maintain Immune Tolerance to Nickel in Healthy, Nonallergic Individuals J. Immunol., December 1, 2003; 171(11): 5760 - 5768. [Abstract] [Full Text] [PDF] |
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K. J. Young, L. S. Kay, M. J. Phillips, and L. Zhang Antitumor Activity Mediated by Double-Negative T Cells Cancer Res., November 15, 2003; 63(22): 8014 - 8021. [Abstract] [Full Text] [PDF] |
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F. Ichihara, K. Kono, A. Takahashi, H. Kawaida, H. Sugai, and H. Fujii Increased Populations of Regulatory T Cells in Peripheral Blood and Tumor-Infiltrating Lymphocytes in Patients with Gastric and Esophageal Cancers Clin. Cancer Res., October 1, 2003; 9(12): 4404 - 4408. [Abstract] [Full Text] [PDF] |
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G. G. Laport, B. L. Levine, E. A. Stadtmauer, S. J. Schuster, S. M. Luger, S. Grupp, N. Bunin, F. J. Strobl, J. Cotte, Z. Zheng, et al. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation Blood, September 15, 2003; 102(6): 2004 - 2013. [Abstract] [Full Text] [PDF] |
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G. Q. Phan, J. C. Yang, R. M. Sherry, P. Hwu, S. L. Topalian, D. J. Schwartzentruber, N. P. Restifo, L. R. Haworth, C. A. Seipp, L. J. Freezer, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma PNAS, July 8, 2003; 100(14): 8372 - 8377. [Abstract] [Full Text] [PDF] |
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K. Sato, N. Yamashita, M. Baba, and T. Matsuyama Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells Blood, May 1, 2003; 101(9): 3581 - 3589. [Abstract] [Full Text] [PDF] |
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T. Bonnefoix, P. Bonnefoix, J.-Q. Mi, J.-J. Lawrence, J.-J. Sotto, and D. Leroux Detection of Suppressor T Lymphocytes and Estimation of Their Frequency in Limiting Dilution Assays by Generalized Linear Regression Modeling J. Immunol., March 15, 2003; 170(6): 2884 - 2894. [Abstract] [Full Text] [PDF] |
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R. K. Batra, Y. Lin, S. Sharma, M. Dohadwala, J. Luo, M. Pold, and S. M. Dubinett Non-Small Cell Lung Cancer-derived Soluble Mediators Enhance Apoptosis in Activated T Lymphocytes through an I{kappa}B Kinase-dependent Mechanism Cancer Res., February 1, 2003; 63(3): 642 - 646. [Abstract] [Full Text] [PDF] |
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A. M. Wolf, D. Wolf, M. Steurer, G. Gastl, E. Gunsilius, and B. Grubeck-Loebenstein Increase of Regulatory T Cells in the Peripheral Blood of Cancer Patients Clin. Cancer Res., February 1, 2003; 9(2): 606 - 612. [Abstract] [Full Text] [PDF] |
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W.-P. Min, D. Zhou, T. E. Ichim, G. H. Strejan, X. Xia, J. Yang, X. Huang, B. Garcia, D. White, P. Dutartre, et al. Inhibitory Feedback Loop Between Tolerogenic Dendritic Cells and Regulatory T Cells in Transplant Tolerance J. Immunol., February 1, 2003; 170(3): 1304 - 1312. [Abstract] [Full Text] [PDF] |
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C. J. Moran, D. A. Arenberg, C.-C. Huang, T. J. Giordano, D. G. Thomas, D. E. Misek, G. Chen, M. D. Iannettoni, M. B. Orringer, S. Hanash, et al. RANTES Expression Is a Predictor of Survival in Stage I Lung Adenocarcinoma Clin. Cancer Res., December 1, 2002; 8(12): 3803 - 3812. [Abstract] [Full Text] [PDF] |
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R. Somasundaram, L. Jacob, R. Swoboda, L. Caputo, H. Song, S. Basak, D. Monos, D. Peritt, F. Marincola, D. Cai, et al. Inhibition of Cytolytic T Lymphocyte Proliferation by Autologous CD4+/CD25+ Regulatory T Cells in a Colorectal Carcinoma Patient Is Mediated by Transforming Growth Factor-{beta} Cancer Res., September 15, 2002; 62(18): 5267 - 5272. [Abstract] [Full Text] [PDF] |
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