{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T17:50:13Z","timestamp":1767203413421,"version":"build-2238731810"},"reference-count":39,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["RC-2022-2773380"],"award-info":[{"award-number":["RC-2022-2773380"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Background. Classical Hodgkin\u2019s lymphoma (cHL) in adolescents between 15 and 18 years old shows a higher disease-related mortality, and the overall prognosis is worse than in both children and adults. Objectives. We investigated the immune checkpoint inhibitors (ICPIs) therapeutic targets and specific T-regulatory and cytotoxic T-cell subsets in the subgroup of adolescent cHL patients, and we challenged their prognostic power. Methods. We retrieved formalin-fixed paraffin-embedded (FFPE) tissue of adolescent patients diagnosed with cHL and tested by immunohistochemistry the immune checkpoint molecules CTLA-4, LAG-3, PD-1, and PDL1 as well as the biological markers FOXP3 and CD8. Results. All the cases of our cohort expressed the immune checkpoint molecules CTLA-4, LAG-3, and PD-1 in microenvironment (ME), and the number of PD1+ cells was strongly associated with advanced disease, being higher in stage III\/IV, indicating a possible role in the progression of cHL. A higher risk of recurrence and progression occurred in patients with lower amount of CD8+ microenvironmental T-cells at diagnosis (67.14 \u00b1 27.23 vs. 42.86 \u00b1 17.33 p = 0.032 and 65.59 \u00b1 26.68 vs. 37 \u00b1 17.45 p = 0.046, respectively). Conclusions. We showed that microenvironment of cHL in adolescent patients is enriched with potential therapeutic targets of ICPI that may be considered for therapeutic applications. Furthermore, the presence of PD-1 expressing T-cells strongly relates to advanced stage disease and a low density of CD8+ T lymphocytes is associated with recurrence and progression of disease.<\/jats:p>","DOI":"10.3390\/cancers16244210","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T03:40:56Z","timestamp":1734493256000},"page":"4210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microenvironmental Traits of Classical Hodgkin\u2019s Lymphoma in Adolescents and Their Prognostic Impact"],"prefix":"10.3390","volume":"16","author":[{"given":"Clara","family":"Bertuzzi","sequence":"first","affiliation":[{"name":"Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Righi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5593-5397","authenticated-orcid":false,"given":"Giovanna","family":"Motta","sequence":"additional","affiliation":[{"name":"Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Carella","sequence":"additional","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1162-8712","authenticated-orcid":false,"given":"Giulia","family":"Gabrielli","sequence":"additional","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Facchini","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-394X","authenticated-orcid":false,"given":"Maurizio","family":"Baldassarre","sequence":"additional","affiliation":[{"name":"Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arcangelo","family":"Prete","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-2651","authenticated-orcid":false,"given":"Pier","family":"Zinzani","sequence":"additional","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-220X","authenticated-orcid":false,"given":"Massimo","family":"Mascolo","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Pathology Section, School of Medicine, University of Naples, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4945-1422","authenticated-orcid":false,"given":"Claudio","family":"Agostinelli","sequence":"additional","affiliation":[{"name":"Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-3591","authenticated-orcid":false,"given":"Elena","family":"Sabattini","sequence":"additional","affiliation":[{"name":"Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1200\/JCO.1997.15.8.2769","article-title":"Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin\u2019s disease in pediatric patients: A Pediatric Oncology Group study","volume":"15","author":"Weiner","year":"1997","journal-title":"J. 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