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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3226-3233. Prepublished online as a Blood First Edition Paper on July 20, 2007; DOI 10.1182/blood-2006-12-064360. This Article Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: blood-2006-12-064360v1 110/9/3226    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chemnitz, J. M Articles by Schultze, J. L Search for Related Content PubMed PubMed Citation Articles by Chemnitz, J. M Articles by Schultze, J. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 21, 2006 Accepted July 10, 2007 RNA-fingerprints provide direct evidence for the inhibitory role of TGF and PD-1 on CD4+ T cells in Hodgkin's lymphoma Jens M Chemnitz, Daniela Eggle, Julia Driesen, Sabine Classen, James L Riley, Svenja Debey-Pascher, Marc Beyer, Alexey Popov, Thomas Zander, and Joachim L Schultze* Molecular Tumor Biology & Tumor Immunology, Department of Internal Medicine I, University of Cologne, Cologne, Germany Abramson Cancer Research Center, University of Pennsylvania, Philadelphia, PA, United States * Corresponding author; email: joachim.schultze{at}uk-koeln.de. A hallmark of various human malignancies is the expression of immunoinhibitory factors within the tumor microenvironment. There is indirect evidence based on in vitro experiments that tumor-infiltrating T cells in human malignancies are suppressed by such factors. Still, direct evidence of the influence of individual inhibitory factors on immune cells in human cancer in vivo is lacking. To address this question we used Hodgkin's lymphoma (HL) as a model since histopathological characteristics of HL are thought to be mostly due to the effects of a wide variety of cytokines, including TGF or membrane bound receptors like PD-1 which are suspected to contribute to immune evasion of tumor cells. Using a genome-wide transcriptional approach we established specific RNA-fingerprints of TGF and PD-1 signaling in human T cells in vitro. Applying these specific fingerprints we directly demonstrate that CD4+ T cells in HL - but not in follicular lymphoma (FL)- are under the inhibitory influence of both TGF and PD-1 in vivo. This approach can be easily generalized to provide direct evidence of the impact of any given soluble or cell-bound factor on any cell type within diseased tissue. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Beyer, J. Karbach, M. R. Mallmann, T. Zander, D. Eggle, S. Classen, S. Debey-Pascher, M. Famulok, E. Jager, and J. L. Schultze Cancer Vaccine Enhanced, Non-Tumor-Reactive CD8+ T Cells Exhibit a Distinct Molecular Program Associated with "Division Arrest Anergy" Cancer Res., May 15, 2009; 69(10): 4346 - 4354. [Abstract] [Full Text] [PDF] R. Yamamoto, M. Nishikori, T. Kitawaki, T. Sakai, M. Hishizawa, M. Tashima, T. Kondo, K. Ohmori, M. Kurata, T. Hayashi, et al. PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma Blood, March 15, 2008; 111(6): 3220 - 3224. [Abstract] [Full Text] [PDF] K. L. Alderson, Q. Zhou, V. Berner, D. E. C. Wilkins, J. M. Weiss, B. R. Blazar, L. A. Welniak, R. H. Wiltrout, D. Redelman, and W. J. Murphy Regulatory and Conventional CD4+ T Cells Show Differential Effects Correlating with PD-1 and B7-H1 Expression after Immunotherapy J. Immunol., March 1, 2008; 180(5): 2981 - 2988. [Abstract] [Full Text] [PDF]

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