{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:22:50Z","timestamp":1791976970311,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,5,19]],"date-time":"2015-05-19T00:00:00Z","timestamp":1431993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"crossref","award":["MOST-103-2320-B-006-020-MY3"],"award-info":[{"award-number":["MOST-103-2320-B-006-020-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004844","name":"National Cheng Kung University Hospital, Taiwan","doi-asserted-by":"crossref","award":["NCKUH-10104006"],"award-info":[{"award-number":["NCKUH-10104006"]}],"id":[{"id":"10.13039\/501100004844","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Primary central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) diffuse large B\u2010cell lymphoma (<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>) is an ominous disease with a poor prognosis. The brain is an immune\u2010privileged sanctuary, and this may contribute to an ineffective host immune response and thus a poorer outcome. The aim of this study was therefore to study the difference in the immune composition in<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>and non\u2010<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>diffuse large B\u2010cell lymphoma (<jats:styled-content style=\"fixed-case\">DLBCL<\/jats:styled-content>), and the role of the immune response in<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Thirty\u2010two biopsy specimens of<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>and 30 specimens of low\u2010stage non\u2010<jats:styled-content style=\"fixed-case\">CNS DLBCL<\/jats:styled-content>from immunocompetent patients formed the study group. The density and distribution of immune cells, including dendritic cells (dendritic cell\u2010specific lysosomal\u2010associated membrane protein\u2010positive and S100\u2010positive), effector\/memory T cells (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>45<jats:styled-content style=\"fixed-case\">RO<\/jats:styled-content>\u2010positive), and cytotoxic T cells (granzyme B\u2010positive), and the expression of<jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>by lymphoma cells, were evaluated immunohistochemically.<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>patients showed poorer overall survival (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.032). On comparison of the<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">DLBCL<\/jats:styled-content>biopsy specimens, the<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>cells showed less<jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DR<\/jats:styled-content>expression (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003), and there were fewer S100\u2010positive cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01), and effector T cells (<jats:italic>P<\/jats:italic>\u00a0= 0.026) infiltrating<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>than infiltrating<jats:styled-content style=\"fixed-case\">DLBCL<\/jats:styled-content>. For<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>patients, fewer cytotoxic T cells in the background constituted a poor prognostic factor (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.004). Intratumoral S100\u2010positive cell infiltration was positively correlated with T\u2010cell infiltration, and a T\u2010cell rimming pattern.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>, the baseline antitumour immune response is less as compared with non\u2010<jats:styled-content style=\"fixed-case\">CNS DLBCL<\/jats:styled-content>, and this response may play a role in the poorer prognosis. Adjuvant dendritic cell and T\u2010cell immunotherapy may further boost treatment responses in<jats:styled-content style=\"fixed-case\">PCNSL<\/jats:styled-content>patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12706","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T14:29:20Z","timestamp":1427898560000},"page":"625-635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Primary central nervous system diffuse large B\u2010cell lymphoma has poorer immune cell infiltration and prognosis than its peripheral counterpart"],"prefix":"10.1111","volume":"67","author":[{"given":"Chen","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Pathology College of Medicine National Cheng Kung University and Hospital Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Hung","family":"Lin","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Internal Medicine National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann\u2010Lii","family":"Cheng","sequence":"additional","affiliation":[{"name":"Departments of Oncology and Internal Medicine National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L Jeffrey","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kung\u2010Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology College of Medicine National Cheng Kung University and Hospital Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-010-0269-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199501000-00016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not151"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23551"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-321349"},{"key":"e_1_2_8_7_1","first-page":"630","volume-title":"Immunobiology: the immune system in health and disease","author":"Janeway CA","year":"2005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-02-137372"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.009647"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1249481"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1339"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.3685"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.767"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.3.720"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2890"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2365"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198909283211302"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.10.3569"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.245"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0504"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00098"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.51.93"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1783"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1699"},{"key":"e_1_2_8_25_1","first-page":"233","volume-title":"World Health Organization classification of tumours of haematopoietic and lymphoid tissues","author":"Swerdlow SH","year":"2008"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2947"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1545"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21979"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/52.3-4.650"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","article-title":"Regression models and life tables","volume":"34","author":"Cox DR","year":"1972","journal-title":"J. R. Stat. Soc. Series B. Stat. Methodol."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27381"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309303291402"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.07.155"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403240"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06593.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-008-0028-z"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.5.755"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2007.06661.x"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.09.139"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0113"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.30.0368"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000076"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp505"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11702"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1024"},{"key":"e_1_2_8_47_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1182\/blood.V82.6.1803.1803","article-title":"Lysis of malignant B cells from patients with B\u2010chronic lymphocytic leukemia by autologous T cells activated with CD3\u00a0\u00d7\u00a0CD19 bispecific antibodies in combination with bivalent CD28 antibodies","volume":"82","author":"Bohlen H","year":"1993","journal-title":"Blood"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20417"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10673"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9414-8"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1018-0"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7554"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10225"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00538-2"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.12706","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.12706","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T03:54:23Z","timestamp":1717818863000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.12706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,19]]},"references-count":53,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1111\/his.12706"],"URL":"https:\/\/doi.org\/10.1111\/his.12706","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,19]]},"assertion":[{"value":"2014-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}