{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:55:06Z","timestamp":1792086906890,"version":"4.4.0"},"reference-count":32,"publisher":"American Society of Hematology","issue":"25","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Classic Hodgkin lymphoma (cHL) is the cancer type most susceptible to antibodies targeting programmed cell death protein 1 (PD1) and is characterized by scarce Hodgkin and Reed-Sternberg cells (HRSCs), perpetuating a unique tumor microenvironment (TME). Although anti-PD1 effects appear to be largely mediated by cytotoxic CD8+ T cells in solid tumors, HRSCs frequently lack major histocompatibility complex expression, and the mechanism of anti-PD1 efficacy in cHL is unclear. Rapid clinical responses and high interim complete response rates to anti-PD1 based first-line treatment were recently reported for patients with early-stage unfavorable cHL treated in the German Hodgkin Study Group phase 2 NIVAHL trial. To investigate the mechanisms underlying this very early response to anti-PD1 treatment, we analyzed paired biopsies and blood samples obtained from NIVAHL patients before and during the first days of nivolumab first-line cHL therapy. Mirroring the rapid clinical response, HRSCs had disappeared from the tissue within days after the first nivolumab application. The TME already shows a reduction in type 1 regulatory T cells and PD-L1+ tumor-associated macrophages at this early time point of treatment. Interestingly, a cytotoxic immune response and a clonal T-cell expansion were not observed in the tumors or peripheral blood. These early changes in the TME were distinct from alterations found in a separate set of cHL biopsies at relapse during anti-PD1 therapy. We identify a unique very early histologic response pattern to anti-PD1 therapy in cHL that is suggestive of withdrawal of prosurvival factors, rather than induction of an adaptive antitumor immune response, as the main mechanism of action.<\/jats:p>","DOI":"10.1182\/blood.2020008553","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T16:57:32Z","timestamp":1603904252000},"page":"2851-2863","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":68,"title":["Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-4030","authenticated-orcid":false,"given":"Sarah","family":"Reinke","sequence":"first","affiliation":[{"name":"Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9662-9900","authenticated-orcid":false,"given":"Paul J.","family":"Br\u00f6ckelmann","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf (CIO ABCD) and German Hodgkin Study Group (GHSG), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7324-993X","authenticated-orcid":false,"given":"Ingram","family":"Iaccarino","sequence":"additional","affiliation":[{"name":"Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-5942","authenticated-orcid":false,"given":"Maria","family":"Garcia-Marquez","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine, Cologne Translational Immunology, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Borchmann","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf (CIO ABCD) and German Hodgkin Study Group (GHSG), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Jochims","sequence":"additional","affiliation":[{"name":"Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-1072","authenticated-orcid":false,"given":"Michaela","family":"Kotrova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-4691","authenticated-orcid":false,"given":"Karol","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5514-5010","authenticated-orcid":false,"given":"Monika","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2134-2774","authenticated-orcid":false,"given":"Elena","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of W\u00fcrzburg, W\u00fcrzburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Sasse","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne D\u00fcsseldorf (CIO ABCD) and German Hodgkin Study Group (GHSG), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany;"},{"name":"Clinic for Hematology and Medical Oncology, University Medicine G\u00f6ttingen, G\u00f6ttingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Kobe","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and German Hodgkin Study Group, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Mathas","sequence":"additional","affiliation":[{"name":"Hematology, Oncology, and Tumor Immunology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Max-Delbr\u00fcck-Center for Molecular Medicine, Berlin, Germany;"},{"name":"German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Soekler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University of T\u00fcbingen, T\u00fcbingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Keller","sequence":"additional","affiliation":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin, Campus Benjamin Franklin, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bormann","sequence":"additional","affiliation":[{"name":"Medical Department I, Klinikum Bremen-Mitte, Bremen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Ludwigs-Maximilians-Universit\u00e4t (LMU) Munich and Comprehensive Cancer Center (CCC) \/German Cancer Consortium (DKTK)\/Bayerisches Zentrum f\u00fcr Krebsforschung (BZKF), Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Richter","sequence":"additional","affiliation":[{"name":"Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, 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