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Blood, 19 November 2009, Vol. 114, No. 21, pp. 4713-4720. Prepublished online as a Blood First Edition Paper on September 28, 2009; DOI 10.1182/blood-2009-04-217687. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-04-217687v1 114/21/4713    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Ramsay, A. G. Articles by Gribben, J. G. PubMed PubMed Citation Articles by Ramsay, A. G. Articles by Gribben, J. G. Related Collections Immunobiology Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy Alan G. Ramsay1, Andrew J. Clear1, Gavin Kelly2, Rewas Fatah1, Janet Matthews1, Finlay MacDougall1, T. Andrew Lister1, Abigail M. Lee3, Maria Calaminici3, and John G. Gribben1 1 Institute of Cancer, Cancer Research UK Clinical Centre for Medical Oncology, Barts and The London School of Medicine, Queen Mary University of London, London; 2 Bioinformatics and Biostatistics Service, Cancer Research UK, London; and 3 Cellular Pathology, Barts and The London National Health Service Trust, London, United Kingdom An important hallmark of cancer progression is the ability of tumor cells to evade immune recognition. Understanding the relationship between neoplastic cells and the immune microenvironment should facilitate the design of improved immunotherapies. Here we identify impaired T-cell immunologic synapse formation as an active immunosuppressive mechanism in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). We found a significant reduction in formation of the F-actin immune synapse in tumor-infiltrating T cells (P < .01) from lymphoma patients compared with age-matched healthy donor cells. Peripheral blood T cells exhibited this defect only in patients with leukemic-phase disease. Moreover, we demonstrate that this T-cell defect is induced after short-term tumor cell contact. After 24-hour coculture with FL cells, previously healthy T cells showed suppressed recruitment of critical signaling proteins to the synapse. We further demonstrate repair of this defect after treatment of both FL cells and T cells with the immunomodulatory drug lenalidomide. Tissue microarray analysis identified reduced expression of the T-cell synapse signature proteins, including the cytolytic effector molecule Rab27A associated with poor prognosis, in addition to reduced T-cell numbers and activity with disease transformation. Our results highlight the importance of identifying biomarkers and immunotherapeutic treatments for repairing T-cell responses in lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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