{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:10:40Z","timestamp":1791526240677,"version":"4.3.4"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T00:00:00Z","timestamp":1585958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["311171"],"award-info":[{"award-number":["311171"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish Cancer Organizations","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100007797","name":"Helsingin Yliopisto","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007797","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008376","name":"Helsingin ja Uudenmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","award":["TYH2015401"],"award-info":[{"award-number":["TYH2015401"]}],"id":[{"id":"10.13039\/100008376","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007083","name":"Orionin Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Finnish Society for Oncology","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Tumor microenvironment and immune escape affect pathogenesis and survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants with clinical impact have remained undefined. Here, we have used multiplex immunohistochemistry and digital image analysis to characterize TAM immunophenotypes with regard to expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1) from the diagnostic tumor tissue samples of 130 cHL patients, and correlated the findings with clinical characteristics and survival. We show that a large proportion of TAMs express PD-L1 (CD68+, median 32%; M2 type CD163+, median 22%), whereas the proportion of TAMs expressing IDO-1 is lower (CD68+, median 5.5%; CD163+, median 1.4%). A high proportion of PD-L1 and IDO-1 expressing TAMs from all TAMs (CD68+), or from CD163+ TAMs, is associated with inferior outcome. In multivariate analysis with age and stage, high proportions of PD-L1+ and IDO-1+ TAMs remain independent prognostic factors for freedom from treatment failure (PD-L1+CD68+\/CD68+, HR = 2.63, 95% CI 1.17\u20135.88, p = 0.019; IDO-1+CD68+\/CD68+, HR = 2.48, 95% CI 1.03\u20135.95, p = 0.042). In contrast, proportions of PD-L1+ tumor cells, all TAMs or PD-L1\u2212 and IDO-1\u2212 TAMs are not associated with outcome. The findings implicate that adverse prognostic impact of TAMs is checkpoint-dependent in cHL.<\/jats:p>","DOI":"10.3390\/cancers12040877","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T03:58:39Z","timestamp":1586231919000},"page":"877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Kristiina","family":"Karihtala","sequence":"first","affiliation":[{"name":"Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3224-0757","authenticated-orcid":false,"given":"Suvi-Katri","family":"Leivonen","sequence":"additional","affiliation":[{"name":"Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7842-9419","authenticated-orcid":false,"given":"Oscar","family":"Br\u00fcck","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja-Liisa","family":"Karjalainen-Lindsberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, Helsinki University Hospital, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-8241","authenticated-orcid":false,"given":"Satu","family":"Mustjoki","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teijo","family":"Pellinen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland (FIMM), 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8265-511X","authenticated-orcid":false,"given":"Sirpa","family":"Lepp\u00e4","sequence":"additional","affiliation":[{"name":"Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland"},{"name":"Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, 00029 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3324\/haematol.2015.132761","article-title":"The immune microenvironment in Hodgkin lymphoma: T cells, B cells, and immune checkpoints","volume":"101","author":"Vardhana","year":"2016","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1200\/JCO.2010.32.8401","article-title":"Molecular pathogenesis of Hodgkin\u2019s lymphoma: Increasing evidence of the importance of the microenvironment","volume":"29","author":"Steidl","year":"2011","journal-title":"J. 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