{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T01:30:57Z","timestamp":1793669457150,"version":"4.5.1"},"reference-count":67,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin-6 (IL-6) can induce therapeutic resistance for several cancer agents currently used to treat classical Hodgkin lymphoma (cHL). We aimed to investigate whether the presence of IL-6+ leukocytes and IL-6+ Hodgkin-Reed-Sternberg (HRS) cells in the tumor microenvironment (TME) was associated with adverse survival outcomes, expression of other immune markers, and serum IL-6 levels. We used a contemporarily treated cohort (n = 136), with a median follow-up of 13.8 years (range, 0.59-15.9 years). We performed immunohistochemistry with an IL-6 antibody on tissue microarrays from diagnostic biopsies of cHL patients. Patients with IL-6+ leukocytes \u22651% (n = 54 of 136) had inferior event-free survival (hazard ratio [HR] = 3.58; 95% confidence interval [CI], 1.80-7.15) and overall survival (HR = 6.71; 95% CI, 2.51-17.99). The adverse survival was maintained in multivariate Cox regression and propensity score-matched analyses, adjusting for well-known poor-prognostic covariates. The presence of IL-6+ HRS cells and high serum IL-6 levels were not associated with survival. IL-6+ leukocytes correlated with increased proportions of IL-6+ HRS cells (P &amp;lt; .01), CD138+ plasma cells (P &amp;lt; .01), CD68+ macrophages (P = .02), and tryptase-positive mast cells (P &amp;lt; .01). IL-6+ HRS cells correlated with increased proportions of CD68+ macrophages (P = .03), programmed death-ligand 1\u2013positive (PD-L1+) leukocytes (P = .04), and PD-L1+ HRS cells (P &amp;lt; .01). Serum-IL-6 lacked correlation with IL-6 expression in the TME. This is the first study highlighting the adverse prognostic impact of IL-6+ leukocytes in the TME in a cohort of contemporarily treated adult patients with cHL.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003664","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T11:35:27Z","timestamp":1615808127000},"page":"1671-1681","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":34,"title":["Revisiting IL-6 expression in the tumor microenvironment of classical Hodgkin lymphoma"],"prefix":"10.1182","volume":"5","author":[{"given":"Alex Reza","family":"Gholiha","sequence":"first","affiliation":[{"name":"Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0226-5681","authenticated-orcid":false,"given":"Peter","family":"Hollander","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6158-3041","authenticated-orcid":false,"given":"Ingrid","family":"Glimelius","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustaf","family":"Hedstrom","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Molin","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hjalgrim","sequence":"additional","affiliation":[{"name":"Section of Epidemiology Research, Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark;"},{"name":"Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin E.","family":"Smedby","sequence":"additional","affiliation":[{"name":"Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; and"},{"name":"Department of Hematology, Karolinska University Hospital, Stockholm, 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