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Herein, different immune signatures are characterized and correlated with treatment outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tumor\u2010infiltrating leukocytes were phenotyped in biopsies from 459 patients with <jats:styled-content style=\"fixed-case\">cHL<\/jats:styled-content>. Time to progression (<jats:styled-content style=\"fixed-case\">TTP<\/jats:styled-content>) (primary progression, relapse, or death from <jats:styled-content style=\"fixed-case\">cHL<\/jats:styled-content>) and overall survival were analyzed using Cox proportional hazards regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The leukocyte infiltration in the microenvironment was highly diverse between patients and was categorized in 4 immune signatures (active, anergic, innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter <jats:styled-content style=\"fixed-case\">TTP<\/jats:styled-content> (median 12.9\u2010year follow\u2010up) in age\u2010adjusted analyses (hazard ratio\u00a0=\u00a01.82; 95% confidence interval 1.05\u20103\u201015). Epstein\u2010Barr virus (<jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>)\u2010positive cases had higher proportions of macrophages and activated lymphocytes than <jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content> negative, but neither of those leukocytes predicted prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Abundant Tregs (anergic signature) indicate a shorter <jats:styled-content style=\"fixed-case\">TTP<\/jats:styled-content>, particularly in younger patients. This is probably due to a reduced ability of the immune system to attack the tumor cells. Our data warrant further investigation if these suggested immune signatures could predict outcome of immunotherapy such as immune checkpoint inhibitors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12987","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T13:42:44Z","timestamp":1508852564000},"page":"88-97","source":"Crossref","is-referenced-by-count":26,"title":["An anergic immune signature in the tumor microenvironment of classical Hodgkin lymphoma is associated with inferior outcome"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0226-5681","authenticated-orcid":false,"given":"Peter","family":"Hollander","sequence":"first","affiliation":[{"name":"Experimental and Clinical Oncology Department of Immunology, Genetics and Pathology Uppsala University  Uppsala 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