{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:46:22Z","timestamp":1790480782650,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T00:00:00Z","timestamp":1628812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epstein\u2010Barr virus (EBV) is detected in a variety of B\u2010cell lymphomas (BCLs) and B\u2010cell lymphoproliferative disorders (B\u2010LPDs). Immunodeficiency has been considered to play a key role in the pathogenesis of these diseases. In addition, immune escape of tumor cells may also contribute to the development of EBV<jats:sup>+<\/jats:sup> BCLs and B\u2010LPDs. The PD\u20101\/PD\u2010L1 pathway is particularly important for immune escape of tumor cells that contribute to development of lymphoma through suppression of cytotoxic T\u2010cell function. We now consider PD\u2010L1 immunohistochemistry (IHC) a very useful method for predicting whether tumor cells of lymphoid malignancies are characterized by the immune escape mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We reviewed articles of EBV<jats:sup>+<\/jats:sup> BCLs and B\u2010LPDs from the perspective of immune escape and immunodeficiency, particularly focusing on PD\u2010L1 IHC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on PD\u2010L1 IHC, we consider that EBV<jats:sup>+<\/jats:sup> BCL and B\u2010LPD can be classified into three types: \u201cimmunodeficiency\u201d, \u201cimmune escape\u201d, and \u201cimmunodeficiency + immune escape\u201d type. The immunodeficiency type includes EBV<jats:sup>+<\/jats:sup> diffuse large BCL (DLBCL) of the elderly, EBV<jats:sup>+<\/jats:sup> sporadic Burkitt lymphoma, EBV<jats:sup>+<\/jats:sup> mucocutaneous ulcer, and methotrexate (MTX)\u2010associated B\u2010LPD. The immune escape type includes EBV<jats:sup>+<\/jats:sup> classic Hodgkin lymphoma (CHL) and EBV<jats:sup>+<\/jats:sup> DLBCL of the young. The immunodeficiency + immune escape type includes CHL type MTX\u2010associated LPD and a minor subset of EBV<jats:sup>+<\/jats:sup> DLBCL of the elderly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Recently, good results have been reported for immune check\u2010point inhibitors in treating lymphoma. Lymphomas and LPDs characterized by immune escape are regarded as good candidates for PD1\/PD\u2010L1 blockade therapy. Therefore, from both the clinical and pathological perspective, we suggest that lymphoma diagnosis should be made considering immune escape and immunodeficiency.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4198","type":"journal-article","created":{"date-parts":[[2021,8,13]],"date-time":"2021-08-13T10:46:06Z","timestamp":1628851566000},"page":"6777-6785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["EBV\u2010positive B\u2010cell lymphomas and lymphoproliferative disorders: Review from the perspective of immune escape and immunodeficiency"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-6087","authenticated-orcid":false,"given":"Akira","family":"Satou","sequence":"first","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Nagoya University Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,13]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow S","year":"2017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqw214"},{"key":"e_1_2_8_4_1","first-page":"153","article-title":"B\u2010cell and classical Hodgkin lymphomas associated with immunodeficiency: 2015 SH\/EAHP workshop report\u2010part 2","volume":"147","author":"Jong D","year":"2017","journal-title":"Am J Clin Pathol"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S133385"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090331"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.04.010"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-629600"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-02-698936"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-020-02901-w"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01616-3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3104"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1203486"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.36"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1517"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051848"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810958105"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0310"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2014.93"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.4482"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18294"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09754"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0380-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003689"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2006.11.016"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1046"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens7010028"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-489708"},{"key":"e_1_2_8_31_1","first-page":"S52","article-title":"Drug combinations with methotrexate to treat rheumatoid arthritis","volume":"28","author":"Rath T","year":"2010","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem279"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra032015"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-630632"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200301000-00003"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2823"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2008.00813.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2009.02466.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-323238"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0189-6"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2019.09.005"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1942"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13475"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-508044"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-770719"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0680"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-04-843714"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03741"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.973"},{"key":"e_1_2_8_50_1","first-page":"15","article-title":"Histopathologic features of high\u2010grade non\u2010Hodgkin's lymphomas in acquired immunodeficiency syndrome. The French Study Group of pathology for human immunodeficiency virus\u2010associated tumors","volume":"115","author":"Raphael M","year":"1991","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000332"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23187"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0855"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181cf8622"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0599-8"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12745"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13464"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000282"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2015.06.028"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2014.07.009"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2007.107"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001271"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12116"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0264-2"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13249"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqz198"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411087"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-756841"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.9789"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-764209"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30167-X"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.77.3994"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4198","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.4198","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T07:46:35Z","timestamp":1693295195000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.4198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,13]]},"references-count":71,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/cam4.4198"],"URL":"https:\/\/doi.org\/10.1002\/cam4.4198","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,13]]},"assertion":[{"value":"2021-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}