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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1528-1536. Prepublished online as a Blood First Edition Paper on May 6, 2009; DOI 10.1182/blood-2008-09-179697. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-09-179697v1 114/8/1528    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 HighWire Citing Articles via CrossRef Google Scholar Articles by Mumprecht, S. Articles by Ochsenbein, A. F. PubMed PubMed Citation Articles by Mumprecht, S. Articles by Ochsenbein, A. F. Related Collections Immunobiology Myeloid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Programmed death 1 signaling on chronic myeloid leukemia–specific T cells results in T-cell exhaustion and disease progression Sabine Mumprecht1, Christian Schürch1, Juerg Schwaller2, Max Solenthaler3, and Adrian F. Ochsenbein1,4 1 Tumor Immunology, Department of Clinical Research, University of Berne, Berne; 2 Department of Research, Childhood Leukemia, University of Basel, Basel; and 3 Department of Hematology and Central Hematology Laboratory and 4 Institute for Medical Oncology, Inselspital, Berne, Switzerland Chronic myeloid leukemia (CML) is a malignant myeloproliferative disease with a characteristic chronic phase (cp) of several years before progression to blast crisis (bc). The immune system may contribute to disease control in CML. We analyzed leukemia-specific immune responses in cpCML and bcCML in a retroviral-induced murine CML model. In the presence of cpCML and bcCML expressing the glycoprotein of lymphocytic choriomeningitis virus as a model leukemia antigen, leukemia-specific cytotoxic T lymphocytes (CTLs) became exhausted. They maintained only limited cytotoxic activity, and did not produce interferon- or tumor necrosis factor- or expand after restimulation. CML-specific CTLs were characterized by high expression of programmed death 1 (PD-1), whereas CML cells expressed PD-ligand 1 (PD-L1). Blocking the PD-1/PD-L1 interaction by generating bcCML in PD-1–deficient mice or by repetitive administration of PD-L1 antibody prolonged survival. In addition, we found that PD-1 is up-regulated on CD8+ T cells from CML patients. Taken together, our results suggest that blocking the PD-1/PD-L1 interaction may restore the function of CML-specific CTLs and may represent a novel therapeutic approach for CML. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Blocking PD-1 in cancer immunotherapy Gianpietro Dotti Blood 2009 114: 1457-1458. [Abstract] [Full Text] [PDF] This article has been cited by other articles: G. Dotti Blocking PD-1 in cancer immunotherapy Blood, August 20, 2009; 114(8): 1457 - 1458. [Abstract] [Full Text] [PDF]

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