{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:09:31Z","timestamp":1772118571599,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We investigated the intratumoral source of PD\u2010L1 expression and the infiltration of tumor\u2010associated macrophages (TAMs) in large B\u2010cell lymphomas (LBCLs) with or without\n                    <jats:italic>MYC<\/jats:italic>\n                    \u2010translocation, as well as possible correlations to\n                    <jats:italic>BCL2<\/jats:italic>\n                    \u2010and\n                    <jats:italic>BCL6<\/jats:italic>\n                    \u2010translocations and cell of origin (COO). One\u2010hundred and twenty\u2010six patient samples were studied in a cohort enriched for\n                    <jats:italic>MYC<\/jats:italic>\n                    \u2010translocated tumors with 34 samples carrying this translocation. Demonstration of intratumoral distribution and cellular source of PD\u2010L1 was enabled by immunohistochemical (IHC) dual staining specifically highlighting PD\u2010L1 expression in lymphoma B\u2010cells with antibodies against PD\u2010L1 and PAX5. Additional IHC with antibodies against CD68 and CD163 identified TAMs. We found that CD68\u2010positive TAMs were the main source of PD\u2010L1 protein expression in contrast to lymphoma B cells which rarely expressed PD\u2010L1. Semiquantitative IHC demonstrated a significant correlation between CD68 and PD\u2010L1 protein expression. Unsupervised hierarchical analysis of PD\u2010L1, CD68, and CD163 IHC data subsequently demonstrated three potential clusters defined by expression of the three biomarkers. Cluster A consisted of patient samples with significantly lower expression of PD\u2010L1, CD68, and CD163, but also significantly higher prevalence of\n                    <jats:italic>BCL2<\/jats:italic>\n                    \u2010translocation and\n                    <jats:italic>MYC<\/jats:italic>\n                    \u2010\n                    <jats:italic>BCL2<\/jats:italic>\n                    \u2010double\u2010hit (DH) compared to the other two clusters. In cluster C we found a significant accumulation of\n                    <jats:italic>BCL6<\/jats:italic>\n                    translocated tumors. This cluster in contrast had the highest protein expression of PD\u2010L1, CD68, and CD163. Cluster B tumors had an intermediate expression of the three biomarkers, but no accumulation of the specific genetic translocations. Our data, which were based on morphological analysis, immunophenotyping and genotyping by fluorescence in situ hybridization were in line with new concepts of LBCL taxonomy integrating genetic, phenotypical, and immunological characteristics with identification of new subgroups where\n                    <jats:italic>MYC<\/jats:italic>\n                    translocation and\n                    <jats:italic>MYC<\/jats:italic>\n                    \u2010\n                    <jats:italic>BCL2<\/jats:italic>\n                    DH may identify a noninflamed subtype. These findings may furthermore hold significant predictive value especially regarding immune checkpoint blockade therapy, but further molecular characterization should be done to substantiate this hypothesis.\n                  <\/jats:p>","DOI":"10.1002\/hon.2839","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T21:36:26Z","timestamp":1611264986000},"page":"284-292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["High\u2010grade B\u2010cell lymphomas with MYC and BCL2 translocations lack tumor\u2010associated macrophages and PD\u2010L1 expression: A possible noninflamed subgroup"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1204-4807","authenticated-orcid":false,"given":"Marie F.","family":"Breinholt","sequence":"first","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas V. N. P.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias W.","family":"Klausen","sequence":"additional","affiliation":[{"name":"Department of Hematology Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne O.","family":"Gang","sequence":"additional","affiliation":[{"name":"Department of Hematology Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lone","family":"Schejbel","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette \u00d8.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-2511","authenticated-orcid":false,"given":"Mette V.","family":"Elb\u00e6k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Clasen\u2010Linde","sequence":"additional","affiliation":[{"name":"Department of Patologi Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Signe L.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helle","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estrid","family":"H\u00f8gdall","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"N\u00f8rgaard","sequence":"additional","affiliation":[{"name":"Department of Patologi Herlev og Gentofte Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow SH","year":"2017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0016-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.027"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801445"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1090"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.015"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01583"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-629600"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14432"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020602"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0439"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0193-5"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2664"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2012.01787.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13219"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0b013e3180ca8a49"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1545"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12212"},{"key":"e_1_2_7_20_1","volume-title":"31st Annual SAS Users Group International Conference. 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