{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:08:18Z","timestamp":1789016898991,"version":"build-2803163510"},"reference-count":18,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Health Sciences","award":["2019\/061"],"award-info":[{"award-number":["2019\/061"]}]},{"award":["2019\/061"],"award-info":[{"award-number":["2019\/061"]}],"id":[{"id":"https:\/\/ror.org\/03k7bde87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Lymphocyte activation gene-3 (LAG-3) is an inhibitory immune checkpoint molecule that may contribute to immune escape in diffuse large B-cell lymphoma (DLBCL). This study aimed to characterize LAG-3 expression in neoplastic cells and tumor-infiltrating lymphocytes (TILs) and to investigate its associations with clinicopathological features and clinical outcome. Methods: This retrospective, single-center study included 210 patients with DLBCL diagnosed between 2007 and 2019. LAG-3 expression was evaluated immunohistochemically in whole-tissue sections. Tumor-cell expression was assessed according to the percentage and intensity of positive cells, while LAG-3-positive TILs were quantified as the mean number of positive lymphocytes per high-power field (HPF). Associations with clinicopathological parameters, treatment response, overall survival, and progression-free survival (PFS) were analyzed. Results: LAG-3 staining of varying intensity was observed in neoplastic cells in 177 cases (84.3%), and 82 cases (39.0%) were classified as LAG-3 positive using a 10% tumor-cell cut-off. The median number of LAG-3-positive TILs was 5\/HPF. Male patients showed a higher percentage of LAG-3-positive tumor cells than female patients (p = 0.039). Moderate-to-strong tumor-cell staining was significantly more frequent in cases with &gt;5 LAG-3-positive TILs\/HPF than in those with \u22645 TILs\/HPF (p = 0.018). LAG-3 expression parameters were not significantly associated with treatment response or overall survival. Univariate Cox regression analysis also showed no significant association between overall survival and LAG-3-positive TIL count, tumor-cell LAG-3 percentage, or staining intensity. Exploratory PFS analysis in 66 evaluable patients also showed no significant association with LAG-3 expression parameters. Conclusions: LAG-3 expression in DLBCL occurs in both neoplastic cells and TILs. The association between increased LAG-3-positive TILs and stronger tumor-cell expression supports further investigation of LAG-3 across both cellular compartments. No significant association with overall survival was observed in this cohort; however, the limited number of survival events precludes definitive conclusions regarding its prognostic significance. Further studies using standardized assessment methods and larger, clinically well-characterized cohorts are warranted.<\/jats:p>","DOI":"10.3390\/jcm15176888","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"6888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LAG-3 in Diffuse Large B-Cell Lymphoma: Immunohistochemical Expression Patterns and Clinicopathological Correlations"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8806-0400","authenticated-orcid":false,"given":"Mehmet","family":"Do\u011fan","sequence":"first","affiliation":[{"name":"Department of Pathology, Ankara Bilkent City Hospital, Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University, Ankara 06800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine Beg\u00fcm","family":"Co\u015fkun","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Molecular Pathology, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-482X","authenticated-orcid":false,"given":"Mehmet","family":"Bak\u0131rtas\u0327","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tekirda\u011f \u0130smail Fehmi Cumal\u0131o\u011flu City Hospital, Tekirda\u011f 59030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-0135","authenticated-orcid":false,"given":"Ali","family":"Co\u015fkun","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Molecular Pathology, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olcay","family":"Kandemir","sequence":"additional","affiliation":[{"name":"Department of Pathology, Etlik City Hospital, Ankara 06010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70273","DOI":"10.1002\/hem3.70207","article-title":"Large B-Cell Lymphoma (LBCL): EHA Clinical Practice Guidelines for Diagnosis, Treatment, and Follow-Up","volume":"9","author":"Thieblemont","year":"2025","journal-title":"Hemasphere"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1182\/blood-2013-09-524108","article-title":"An Enhanced International Prognostic Index (NCCN-IPI) for Patients with Diffuse Large B-Cell Lymphoma Treated in the Rituximab Era","volume":"123","author":"Zhou","year":"2014","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3324\/haematol.2015.139493","article-title":"Role of the Tumor Microenvironment in Mature B-Cell Lymphoid Malignancies","volume":"101","author":"Fowler","year":"2016","journal-title":"Haematologica"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"38","DOI":"10.21037\/cco-23-124","article-title":"Updates in the Role of the Tumor Microenvironment Cellular Crosstalk and Genetic Signatures in Diffuse Large B-Cell Lymphoma: A Narrative Review","volume":"13","author":"Rastegar","year":"2024","journal-title":"Chin. 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