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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3205-3211. Prepublished online as a Blood First Edition Paper on December 22, 2005; DOI 10.1182/blood-2005-07-2880. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2880v1 107/8/3205    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 Citing Articles via Google Scholar Google Scholar Articles by Godal, R. Articles by Scheibenbogen, C. Search for Related Content PubMed PubMed Citation Articles by Godal, R. Articles by Scheibenbogen, C. Related Collections Immunobiology Neoplasia Signal Transduction Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of bcl-2 Robert Godal, Ulrich Keilholz, Lutz Uharek, Anne Letsch, Anne Marie Asemissen, Antonia Busse, Il-Kang Na, Eckhard Thiel, and Carmen Scheibenbogen From the Department of Internal Medicine, St Elizabeth Oncological Institute, Bratislava, Slovakia; and the Department of Hematology, Oncology, and Transfusion Medicine, Charité, Campus Benjamin Franklin, Berlin, Germany. There is considerable interest in immunotherapeutic approaches for lymphoma. The expression of proteinase inhibitor 9 (PI-9), a molecule that inactivates granzyme B, is considered an immune escape mechanism in lymphoma. Further, lymphomas frequently overexpress the antiapoptotic molecule bcl-2, which is able to inhibit perforin-dependent cytotoxic pathways. In this study, the impact of PI-9 and bcl-2 expression on the sensitivity of lymphomas to T- and natural killer (NK) cell–mediated cytotoxicity was analyzed. We found PI-9 expression in 10 of 18 lymphoma cell lines and in 9 of 14 primary lymphomas. Overexpression of bcl-2 was found in 8 of 18 cell lines and in 12 of 14 primary lymphomas. All lymphoma cells were sensitive to cytolysis by specific T cells and cytokine-activated NK cells, and no difference in sensitivity was observed with respect to PI-9 or bcl-2 expression. Cytolysis was mediated predominantly through perforin-dependent pathways despite expression of PI-9 and bcl-2. Interestingly, the majority of lymphoma cells were resistant to cytolysis by resting allogeneic NK cells. This was due to the failure of lymphomas to induce degranulation of resting NK cells. These results show that resistance to perforin-dependent pathways is not a relevant immune escape mechanism in lymphoma and therefore is unlikely to impair clinical outcome of immunotherapeutic approaches. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Does the serpin PI-9 protect tumor cells? Michael Bots, Rienk Offringa, Jan Paul Medema, Carmen Scheibenbogen, Robert Godal, and Eckhard Thiel Blood 2006 107: 4974-4975. [Full Text] [PDF] This article has been cited by other articles: K. J. Marr, G. J. Jones, C. Zheng, S. M. Huston, M. Timm-McCann, A. Islam, B. M. Berenger, L. L. Ma, J. C. D. Wiseman, and C. H. Mody Cryptococcus neoformans Directly Stimulates Perforin Production and Rearms NK Cells for Enhanced Anticryptococcal Microbicidal Activity Infect. Immun., June 1, 2009; 77(6): 2436 - 2446. [Abstract] [Full Text] [PDF] A. Hamai, F. Meslin, H. Benlalam, A. Jalil, M. Mehrpour, F. Faure, Y. Lecluse, P. Vielh, M.-F. Avril, C. Robert, et al. ICAM-1 Has a Critical Role in the Regulation of Metastatic Melanoma Tumor Susceptibility to CTL Lysis by Interfering with PI3K/AKT Pathway Cancer Res., December 1, 2008; 68(23): 9854 - 9864. [Abstract] [Full Text] [PDF] C. Bossard, K. Belhadj, F. Reyes, N. Martin-Garcia, F. Berger, J. A. Kummer, J. Briere, A.-C. Baglin, S. Cheze, J. Bosq, et al. Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials Blood, March 1, 2007; 109(5): 2183 - 2189. [Abstract] [Full Text] [PDF] B. Jahrsdorfer, S. E. Blackwell, J. E. Wooldridge, J. Huang, M. W. Andreski, L. S. Jacobus, C. M. Taylor, and G. J. Weiner B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation Blood, October 15, 2006; 108(8): 2712 - 2719. [Abstract] [Full Text] [PDF] M. Bots, R. Offringa, J. P. Medema, C. Scheibenbogen, R. Godal, and E. Thiel Does the serpin PI-9 protect tumor cells? Blood, June 15, 2006; 107(12): 4974 - 4975. [Full Text] [PDF]

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