{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:30:21Z","timestamp":1790836221819,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSC) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) in the vicinity of HRSC express similar regulatory mechanisms in parallel, and their presence in tissue is associated with inferior patient outcomes. MNPs in cHL have hitherto been identified with a small number of canonical markers and are usually described as 'tumor-associated macrophages'. The organization of MNP networks and interactions with HRSC remains unexplored at high resolution. Here, we defined the global immune cell composition of cHL and non-lymphoma lymph nodes, integrating data across single-cell RNA sequencing, spatial transcriptomics, and multiplexed immunofluorescence. We observed that MNPs comprise multiple subsets of monocytes, macrophages and dendritic cells (DCs). Classical monocytes, macrophages and conventional DC2 were enriched in the vicinity of HRSC, but plasmacytoid DCs and activated DCs were excluded. Unexpectedly, cDCs and monocytes expressed immunoregulatory checkpoints PD-L1, TIM-3, and the tryptophan-catabolizing protein IDO, at the same level as macrophages. Expression of these molecules increased with age. We also found that classical monocytes are important signaling hubs, potentially controlling the retention of cDC2 and ThExh via CCR1-, CCR4-, CCR5-, and CXCR3-dependent signaling. Enrichment of the cDC2-monocyte-macrophage network in diagnostic biopsies is associated with early treatment failure. These results reveal unanticipated complexity and spatial polarization within the MNP compartment, further demonstrating their potential roles in immune evasion by cHL.<\/jats:p>","DOI":"10.1182\/blood.2022015575","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T16:18:40Z","timestamp":1675959520000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Spatial and molecular profiling of the mononuclear phagocyte network in Classic Hodgkin lymphoma"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-0085","authenticated-orcid":false,"given":"Benjamin J","family":"Stewart","sequence":"first","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK., United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-6109","authenticated-orcid":false,"given":"Martin","family":"Fergie","sequence":"additional","affiliation":[{"name":"University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Young","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4580-6564","authenticated-orcid":false,"given":"Claire","family":"Jones","sequence":"additional","affiliation":[{"name":"Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7359-7114","authenticated-orcid":false,"given":"Ashwin","family":"Sachdeva","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-822X","authenticated-orcid":false,"given":"Alex E","family":"Blain","sequence":"additional","affiliation":[{"name":"National Horizons Centre, Teesside University, Darlington, DL1 1HG, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8268-2812","authenticated-orcid":false,"given":"Chris M","family":"Bacon","sequence":"additional","affiliation":[{"name":"Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-8949","authenticated-orcid":false,"given":"Vikki","family":"Rand","sequence":"additional","affiliation":[{"name":"School of Health and Life Sciences, Teesside University, Middlesbrough, TS1 3BX, UK., United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Ferdinand","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-0650","authenticated-orcid":false,"given":"Kylie Renee","family":"James","sequence":"additional","affiliation":[{"name":"Garvan Institute of Medical Research, Darlinghurst, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1327-2334","authenticated-orcid":false,"given":"Krishnaa T","family":"Mahbubani","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Elizabeth","family":"Hook","sequence":"additional","affiliation":[{"name":"Cambridge University Hospitals NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK., United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Jonas","sequence":"additional","affiliation":[{"name":"Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Coleman","sequence":"additional","affiliation":[{"name":"Cambridge University Hospitals NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-3696","authenticated-orcid":false,"given":"Kourosh","family":"Saeb-Parsy","sequence":"additional","affiliation":[{"name":"University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Collin","sequence":"additional","affiliation":[{"name":"Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-9828","authenticated-orcid":false,"given":"Menna","family":"Clatworthy","sequence":"additional","affiliation":[{"name":"Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Behjati","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Cambridge, Cambridge, CB2 1QP, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D","family":"Carey","sequence":"additional","affiliation":[{"name":"Newcastle upon Tyne NHS Hospitals Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2023,2,7]]},"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2022015575\/2032988\/blood.2022015575.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2022015575\/2032988\/blood.2022015575.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T16:18:42Z","timestamp":1675959522000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2022015575\/494363\/Spatial-and-molecular-profiling-of-the-mononuclear"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2022015575","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]},"article-number":"blood.2022015575"}}