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Blood, 20 August 2009, Vol. 114, No. 8, pp. 1537-1544. Prepublished online as a Blood First Edition Paper on May 7, 2009; DOI 10.1182/blood-2008-12-195792. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-12-195792v1 114/8/1537    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 Ahmadzadeh, M. Articles by Rosenberg, S. A. PubMed PubMed Citation Articles by Ahmadzadeh, M. Articles by Rosenberg, S. A. Related Collections Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired Mojgan Ahmadzadeh1, Laura A. Johnson1, Bianca Heemskerk1, John R. Wunderlich1, Mark E. Dudley1, Donald E. White1, and Steven A. Rosenberg1 1 Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD Tumor antigen–specific T cells are found within melanomas, yet tumors continue to grow. Although the tumor microenvironment is thought to influence the suppression of tumor-reactive T cells, the underlying mechanisms for this T-cell dysfunction are not clear. Here, we report that the majority of tumor infiltrating T lymphocytes (TIL), including MART-1/Melan-A melanoma antigen–specific CD8 T cells, predominantly expressed PD-1, in contrast to T cells in normal tissues and peripheral blood T lymphocytes (PBL). PD-1+ TIL expressed CTLA-4 and Ki-67, markers that were not expressed by PD-1– TIL and T cells in the normal tissues and PBL. Moreover, PD-1+ TIL were primarily HLA-DR+ and CD127–, in contrast to PD-1– TIL. Effector cytokine production by PD-1+ TIL was impaired compared with PD-1– TIL and PBL. Collectively, the phenotypic and functional characterizations of TIL revealed a significantly higher frequency and level of PD-1 expression on TIL compared with normal tissue T-cell infiltrates and PBL, and PD-1 expression correlated with an exhausted phenotype and impaired effector function. These findings suggest that the tumor microenvironment can lead to up-regulation of PD-1 on tumor-reactive T cells and contribute to impaired antitumor immune responses. 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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