{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:48:04Z","timestamp":1786978084277,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":356,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hodgkin lymphoma (HL) is a neoplastic disease in which the inflammatory microenvironment plays a pivotal role in the tumorigenesis. Neutrophilia is a typical finding in HL at diagnosis and, in particular, in association with lymphocytopenia, is a negative prognostic factor. As the immune checkpoint Programmed Death (PD)-L1\/PD-1 has become an important therapeutic target, we were interested in the expression of PD-L1 in peripheral blood (PB) leukocytes using flow cytometry and RT-PCR in patients with HL and healthy controls. Granulocytes were the major PB cell fraction expressing PD-L1. PD-L1 expression on granulocytes was higher in patients with HL than in controls and correlated with lower T-cell numbers in PB. We analyzed for associations between PD-L1 expression in PB granulocytes at the time of diagnosis with patient characteristics and outcome in 126 patients with HL treated with standard chemotherapy adriamycin, bleomycin, vinblastine, and dacarbazine. Increased PD-L1 expression in PB associated with advanced disease, systemic symptoms, positive interim positron emission tomography, and inferior progression-free survival (PFS). PFS at 4 years was 81% (95% C.I., 71\u201387%) in patients with normal PD-L1 expression and 56% (95% C.I., 35\u201372%) in patients with higher-than-normal PD-L1 expression (p\u00a0=\u00a00.002). In conclusion, PD-L1 expression in PB could become a potentially actionable prognostic factor in HL.<\/jats:p>","DOI":"10.1002\/jlb.5ab0121-041r","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T02:29:40Z","timestamp":1642732180000},"page":"539-545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PD-L1 expression in peripheral blood granulocytes at diagnosis as prognostic factor in classical Hodgkin lymphoma"],"prefix":"10.1093","volume":"112","author":[{"given":"Annarosa","family":"Cuccaro","sequence":"first","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bellesi","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Galli","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Zangrilli","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Corrente","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Cupelli","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Fatone","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Maiolo","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Alma","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Viscovo","sequence":"additional","affiliation":[{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"D'Al\u00f2","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Nucleare, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Martini","sequence":"additional","affiliation":[{"name":"Dipartimento di scienze della salute della donna, del bambino e di sanit\u00e0 pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Anatomia Patologica, Dipartimento di Scienze della vita e sanit\u00e0 pubblica, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Rufini","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Medicina Nucleare, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Giordano","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Medicina Nucleare, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Maria","family":"Larocca","sequence":"additional","affiliation":[{"name":"Dipartimento di scienze della salute della donna, del bambino e di sanit\u00e0 pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Anatomia Patologica, Dipartimento di Scienze della vita e sanit\u00e0 pubblica, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hohaus","sequence":"additional","affiliation":[{"name":"Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS , Rome, IT"},{"name":"Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universit\u00e0 Cattolica del Sacro Cuore Facolt\u00e0 di Medicina e Chirurgia , Rome, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.seminhematol.2016.05.007","article-title":"Hodgkin lymphoma: pathology and biology","volume":"53","author":"Mathas","year":"2016","journal-title":"Semin Hematol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","DOI":"10.4084\/mjhid.2014.053","article-title":"Prognostic factors in Hodgkin lymphoma","volume":"6","author":"Cuccaro","year":"2014","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1056\/NEJM199811193392104","article-title":"A prognostic score for advanced Hodgkin's disease. International prognostic factors project on advanced Hodgkin's Disease","volume":"339","author":"Hasenclever","year":"1998","journal-title":"N Engl J Med"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1309\/AJCPO46GFKGNXCBR","article-title":"Prognostic significance of the ratio of absolute neutrophil count to absolute lymphocyte count in classic hodgkin lymphoma","volume":"138","author":"Koh","year":"2012","journal-title":"Am J Clin Pathol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/hon.2359","article-title":"Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: results of a large multicenter study involving 990 patients","volume":"35","author":"Marcheselli","year":"2017","journal-title":"Hematol Oncol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/bjh.15054","article-title":"Pre-treatment neutrophil\/lymphocyte ratio and platelet\/lymphocyte ratio are prognostic of progression in early stage classical Hodgkin lymphoma","volume":"180","author":"Reddy","year":"2018","journal-title":"Br J Haematol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1007\/s00277-018-3276-y","article-title":"Prognostic meaning of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ration (LMR) in newly diagnosed Hodgkin lymphoma patients treated upfront with a PET-2 based strategy","volume":"97","author":"Romano","year":"2018","journal-title":"Ann Hematol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1158\/1078-0432.CCR-17-0539","article-title":"Immunotherapy of lymphoma and myeloma: facts and hopes","volume":"24","author":"Pianko","year":"2018","journal-title":"Clin Cancer Res"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/PPO.0000000000000331","article-title":"Immunotherapy of Hodgkin lymphoma: mobilizing the patient's immune response","volume":"24","author":"Ansell","year":"2018","journal-title":"Cancer J"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1182\/blood-2010-05-282780","article-title":"Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma","volume":"116","author":"Green","year":"2010","journal-title":"Blood"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1200\/JCO.2016.66.4482","article-title":"PD-L1 and PD-L2 genetic alterations define classical hodgkin lymphoma and predict outcome","volume":"34","author":"Roemer","year":"2016","journal-title":"J Clin Oncol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1182\/blood-2017-03-770719","article-title":"Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma","volume":"130","author":"Carey","year":"2017","journal-title":"Blood"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1182\/bloodadvances.2017006346","article-title":"High proportions of PD-11 and PD-L11 leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcome","volume":"1","author":"Hollander","year":"2017","journal-title":"Blood Adv"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.humpath.2016.03.005","article-title":"Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin and B-cell lymphomas","volume":"54","author":"Menter","year":"2016","journal-title":"Hum Pathol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0072249","article-title":"IFN-\u03b3-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1","volume":"8","author":"de Kleijn","year":"2013","journal-title":"PLoS One"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1189\/jlb.4HI0616-255R","article-title":"Frontline Science: defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1","volume":"100","author":"Patera","year":"2016","journal-title":"J Leukoc Biol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1097\/PPO.0000000000000336","article-title":"Improvements in imaging of hodgkin lymphoma: positron emission tomography","volume":"24","author":"Hutchings","year":"2018","journal-title":"Cancer J"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41590-017-0022-x","article-title":"Myeloid-derived suppressor cells coming of age review-article","volume":"19","author":"Veglia","year":"2018","journal-title":"Nat Immunol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"27676","DOI":"10.18632\/oncotarget.8507","article-title":"Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients","volume":"7","author":"Marini","year":"2016","journal-title":"Oncotarget"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/bjh.13198","article-title":"Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy","volume":"168","author":"Romano","year":"2015","journal-title":"Br J Haematol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"67333","DOI":"10.18632\/oncotarget.12024","article-title":"The prognostic value of the myeloid-mediated immunosuppression marker arginase-1 in classic Hodgkin lymphoma","volume":"7","author":"Romano","year":"2016","journal-title":"Oncotarget"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1136\/gutjnl-2016-313075","article-title":"Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway","volume":"66","author":"Wang","year":"2017","journal-title":"Gut"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1189\/jlb.5MR1216-508R","article-title":"Neutrophils as active regulators of the immune system in the tumor microenvironment","volume":"102","author":"Shaul","year":"2017","journal-title":"J Leukoc Biol"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms20215503","article-title":"Immune and inflammatory cells of the tumor microenvironment represent novel therapeutic targets in classical hodgkin lymphoma","volume":"20","author":"Calabretta","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.1002\/cam4.3396","article-title":"The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: a subanalysis of the prospective phase II PET-2-adapted HD0607 trial","volume":"9","author":"Romano","year":"2020","journal-title":"Cancer Med"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1411087","article-title":"PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma","volume":"372","author":"Ansell","year":"2015","journal-title":"N Engl J Med"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0121546","article-title":"A method for identification and analysis of non-overlapping myeloid immunophenotypes in humans","volume":"10","author":"Gustafson","year":"2015","journal-title":"PLoS One"},{"key":"2023032107561522000_","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1093\/infdis\/jiaa591","article-title":"A granulocytic signature identifies COVID-19 and its severity","volume":"222","author":"Vitte","year":"2020","journal-title":"J Infect Dis"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.5AB0121-041R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.5AB0121-041R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/112\/3\/539\/49469607\/jlb11078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/112\/3\/539\/49469607\/jlb11078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T21:22:26Z","timestamp":1700083346000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/112\/3\/539\/6976197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,1,20]]},"published-print":{"date-parts":[[2022,8,24]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.5ab0121-041r","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2022,1,20]]},"assertion":[{"value":"2021-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}