{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:35:45Z","timestamp":1787027745735,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["20-315-90085"],"award-info":[{"award-number":["20-315-90085"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bristol-Myers Squibb (United Kingdom)","award":["REQ-CA209-8EG"],"award-info":[{"award-number":["REQ-CA209-8EG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed\/refractory (r\/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13\u201363) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163\/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163\/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells p = 0.0086; for CD68-positive cells p = 0.037), while a low number of M2 with higher PFS (p = 0.014). Complete response was associated with a lower level of M2 (p = 0.011). In sequential samples (before and after nivolumab therapy) an increase in PD-1 (p = 0.011) and LAG-3 (p = 0.0045) and a depletion of CD68 (p = 0.057) and CD163 (p = 0.0049)-positive cells were observed. The study expands understanding of the cHL microenvironment structure and dynamics during nivolumab therapy in patients with r\/r cHL.<\/jats:p>","DOI":"10.3390\/cancers13225676","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"5676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed\/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations"],"prefix":"10.3390","volume":"13","author":[{"given":"Artem","family":"Gusak","sequence":"first","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liudmila","family":"Fedorova","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Lepik","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-1444","authenticated-orcid":false,"given":"Nikita","family":"Volkov","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Popova","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Moiseev","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Mikhailova","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Baykov","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-4136","authenticated-orcid":false,"given":"Alexander","family":"Kulagin","sequence":"additional","affiliation":[{"name":"RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, L\u2019va Tolstogo Str. 6-8, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1200\/JCO.2008.19.8820","article-title":"Escalated-Dose BEACOPP in the treatment of patients with advanced-stage hodgkin\u2019s lymphoma: 10 years of follow-up of the GHSG HD9 study","volume":"27","author":"Engert","year":"2009","journal-title":"J. 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