NDLI: Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors.

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Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors.

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Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Medema, J. P. De Jong, J. Albar, J. P. Bres, S. A. Verdegaal, E. M. Offringa, R. Franken, K. L. Hahne, M. Melief, C. J. Peltenburg, L. T. Gorter, A.
Description	Author Affiliation: Medema JP ( Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. medema@mail.medfac.leidenuniv.nl);
Abstract	The concept for cellular immunotherapy of solid tumors relies heavily on the capacity of class I MHC-restricted cytotoxic T lymphocytes (CTLs) to eliminate tumor cells. However, tumors often have managed to escape from the cytolytic machinery of these effector cells. Therefore, it is very important to chart the mechanisms through which this escape can occur. Target-cell killing by CTLs involves the induction of apoptosis by two major mechanisms: through death receptors and the perforin/granzyme B (GrB) pathway. Whereas tumors previously were shown to exhibit mechanisms for blocking the death receptor pathway, we now demonstrate that they also can resist CTL-mediated killing through interference with the perforin/GrB pathway. This escape mechanism involves expression of the serine protease inhibitor PI-9/SPI-6, which inactivates the apoptotic effector molecule GrB. Expression of PI-9 was observed in a variety of human and murine tumors. Moreover, we show that, indeed, expression results in the resistance of tumor cells to CTL-mediated killing both in vitro and in vivo. Our data reveal that PI-9/SPI-6 is an important parameter determining the success of T cell-based immunotherapeutic modalities against cancer.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Membrane Glycoproteins Metabolism Serine Endopeptidases Serine Proteinase Inhibitors Pharmacology Animals Breast Neoplasms Immunology Colonic Neoplasms DNA Primers Flow Cytometry Granzymes Insect Proteins Melanoma Mice Perforin Pore Forming Cytotoxic Proteins Tumor Cells, Cultured Uterine Cervical Neoplasms Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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