{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:16:01Z","timestamp":1792811761736,"version":"4.5.0"},"reference-count":31,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:p>In tumor cells, the serine protease granzyme B is the primary mediator of apoptosis induced by cytotoxic T lymphocytes (CTLs)\/natural killer (NK) cells. The human intracellular serpin proteinase inhibitor 9 (PI9) is the only known human protein able to inhibit the proteolytic activity of granzyme B. When present in the cytoplasm of T lymphocytes, PI9 is thought to protect CTLs against apoptosis induced by their own misdirected granzyme B. Based on the speculation that tumors may also express PI9 to escape CTL\/NK cell surveillance, immunohistochemical studies on the expression of PI9 in various lymphomas were performed. Ninety-two cases of T-cell non-Hodgkin lymphoma (NHL), 75 cases of B-cell NHL, and 57 cases of Hodgkin lymphomas were stained with a PI9-specific monoclonal antibody. In T-cell NHL, highest PI9 expression was found in the extranodal T-cell NHL. In nearly 90% of enteropathy-type T-cell NHLs and 80% of NK\/T-cell, nasal-type lymphomas, the majority of the tumor cells expressed PI9. In nodal T-anaplastic large cell lymphomas and peripheral T-cell lymphomas (not otherwise specified), PI9 expression occurred less frequently. In B-cell NHL, PI9 expression was associated with high-grade malignancy; 43% of diffuse large B-cell lymphomas showed PI9+ tumor cells. Finally, PI9 expression was also found in 10% of Hodgkin lymphomas. This is the first report describing the expression of the granzyme B inhibitor PI9 in human neoplastic cells in vivo. Expression of this inhibitor is yet another mechanism used by tumor cells to escape their elimination by cytotoxic lymphocytes.<\/jats:p>","DOI":"10.1182\/blood.v99.1.232","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"232-237","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":138,"title":["Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: a novel protective mechanism for tumor cells to circumvent the immune system?"],"prefix":"10.1182","volume":"99","author":[{"given":"Bellinda A.","family":"Bladergroen","sequence":"first","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J. L. M.","family":"Meijer","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosita L.","family":"ten Berge","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Erik","family":"Hack","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jettie J. F.","family":"Muris","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny F.","family":"Dukers","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Chott","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kazama","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost J.","family":"Oudejans","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"van Berkum","sequence":"additional","affiliation":[{"name":"From the Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands; Department of Pathophysiology of Plasma Proteins, CLB, Amsterdam, The Netherlands; Department of Clinical Pathology, General Hospital Vienna, Austria; and Department of Pathology, University of New Mexico, Albuquerque."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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