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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1153-1161. Prepublished online as a Blood First Edition Paper on September 28, 2004; DOI 10.1182/blood-2004-03-0791. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0791v1 105/3/1153    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 Bots, M. Articles by Medema, J. P. Search for Related Content PubMed PubMed Citation Articles by Bots, M. Articles by Medema, J. P. Related Collections Immunobiology Apoptosis Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY SPI-CI and SPI-6 cooperate in the protection from effector cell–mediated cytotoxicity Michael Bots, Ingrid G. M. Kolfschoten, Sandra A. Bres, Mirjam T. G. A. Rademaker, Guido M. de Roo, Margreet Krüse, Kees L. M. C. Franken, Michael Hahne, Christopher J. Froelich, Cornelis J. M. Melief, Rienk Offringa, and Jan Paul Medema From the Department of Clinical Oncology, Leiden University Medical Center, The Netherlands; Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands; Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, France; and Department of Medicine, Evanston Northwestern Healthcare Research Institute, IL. Tumors have several mechanisms to escape from the immune system. One of these involves expression of intracellular anticytotoxic proteins that modulate the execution of cell death. Previously, we have shown that the serine protease inhibitor (serpin) SPI-6, which inactivates the cytotoxic protease granzyme B (GrB), is capable of preventing cytotoxic T lymphocyte (CTL)–mediated apoptosis. Despite its potent antiapoptotic activity, SPI-6 does not prevent membranolysis induced by cytotoxic lymphocytes. We now provide evidence that several colon carcinoma cell lines do resist membranolysis and that this protection is dependent on SPI-6 but also requires expression of a closely related serpin called SPI-CI (serine protease inhibitor involved in cytotoxicity inhibition). Expression of SPI-CI is absent from normal colon but observed in placenta, testis, early during embryogenesis, and in cytotoxic lymphocytes. SPI-CI encodes a chymotrypsin-specific inhibitor and irreversibly interacts with purified granzyme M. Moreover, SPI-CI can protect cells from purified perforin/GrM-induced lysis. Our data therefore indicate that SPI-CI is a novel immune escape molecule that acts in concert with SPI-6 to prevent cytotoxic lymphocyte-mediated killing of tumor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Marques, P. S. Hahnel, C. Wolfel, S. Thaler, C. Huber, M. Theobald, and M. Schuler An immune escape screen reveals Cdc42 as regulator of cancer susceptibility to lymphocyte-mediated tumor suppression Blood, February 1, 2008; 111(3): 1413 - 1419. [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] R. Godal, U. Keilholz, L. Uharek, A. Letsch, A. M. Asemissen, A. Busse, I.-K. Na, E. Thiel, and C. Scheibenbogen Lymphomas are sensitive to perforin-dependent cytotoxic pathways despite expression of PI-9 and overexpression of bcl-2 Blood, April 15, 2006; 107(8): 3205 - 3211. [Abstract] [Full Text] [PDF]

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