This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bui, J. D. Articles by Schreiber, R. D. Search for Related Content PubMed PubMed Citation Articles by Bui, J. D. Articles by Schreiber, R. D.

Comparative Analysis of Regulatory and Effector T Cells in Progressively Growing versus Rejecting Tumors of Similar Origins

¹ Center for Immunology, Department of Pathology and Immunology, ² Department of Otolaryngology, and ³ Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri

Requests for reprints: Robert D. Schreiber, Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110. Phone: 314-362-8748; Fax: 314-362-8888; E-mail: schreiber{at}immunology.wustl.edu.

Although regulatory T cells (Tregs) have been detected in clinically apparent and experimentally induced tumors, the significance of their presence is obscured because past studies examined late-stage tumors that had formed in immunocompetent hosts and thus had evolved mechanisms to escape immunologic recognition and/or elimination. Herein, we report the first comparative analysis of the antitumor response to 3'-methylcholanthrene–induced tumors, which either grow progressively (progressor tumors) or are rejected by the immune system (regressor tumors). Surprisingly, we found that both progressor and regressor tumors harbored proliferating (i.e., activated) Foxp3⁺CD25⁺Tregs. However, progressor tumors contained a higher percentage of Tregs in the lymphocyte subset versus regressor tumors. The Tregs in progressor tumors were derived from peripheral CD25⁺ natural Tregs, accumulated early after tumor challenge and were actively proliferating, suggesting that progressor tumors recruited and/or activated endogenous Tregs as a mechanism of escaping immune destruction. To explore whether Tregs directly contributed to the progressive growth phenotype of progressor tumors, we monitored tumor outgrowth in naive wild-type recipients pretreated with either a control monoclonal antibody (mAb) or a depleting CD25-specific mAb. In mice predepleted of CD25⁺ cells, the tumors that subsequently developed displayed an increased accumulation of proliferating CD8⁺ T cells and were rejected. These results show that, although Tregs are activated in both regressor and progressor tumors, the ratio of regulatory to effector T cells is critical in determining whether the host successfully rejects the tumor or eventually succumbs to tumor outgrowth. (Cancer Res 2006; 66(14): 7301-9)

This article has been cited by other articles:

				N. Chaput, G. Darrasse-Jeze, A.-S. Bergot, C. Cordier, S. Ngo-Abdalla, D. Klatzmann, and O. Azogui Regulatory T Cells Prevent CD8 T Cell Maturation by Inhibiting CD4 Th Cells at Tumor Sites J. Immunol., October 15, 2007; 179(8): 4969 - 4978. [Abstract] [Full Text] [PDF]

				T. H. Schreiber The Use of FoxP3 as a Biomarker and Prognostic Factor for Malignant Human Tumors Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 1931 - 1934. [Abstract] [Full Text] [PDF]

				Q. Gao, S.-J. Qiu, J. Fan, J. Zhou, X.-Y. Wang, Y.-S. Xiao, Y. Xu, Y.-W. Li, and Z.-Y. Tang Intratumoral Balance of Regulatory and Cytotoxic T Cells Is Associated With Prognosis of Hepatocellular Carcinoma After Resection J. Clin. Oncol., June 20, 2007; 25(18): 2586 - 2593. [Abstract] [Full Text] [PDF]