{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:52:00Z","timestamp":1782291120468,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: The tumor immune microenvironment, particularly the role of cytotoxic CD8+ T lymphocytes, is crucial in cancer progression but remains poorly understood in pituitary neuroendocrine tumors (PitNETs). The significance of CD8+ cell infiltration varies across PitNET subtypes, suggesting a complex interplay with tumor cell lineage. This study aimed to characterize the distribution of CD8+ tumor-infiltrating lymphocytes across different PitNET subtypes defined by the current WHO classification and to explore their association with clinicopathological features. Methods: We conducted a retrospective study on 40 surgically resected PitNETs. All cases were classified based on immunohistochemical expression of pituitary hormones and lineage-specific transcription factors (PIT-1, TPIT, SF-1). CD8+ lymphocyte density was quantified using immunohistochemistry and calculated as cells\/mm2. Exploratory statistical analysis was performed based on non-parametric tests to compare CD8+ cell density across tumor subtypes and with parameters like tumor size, invasiveness (Knosp grade), and proliferation index (Ki-67). Findings are to be treated as observational trends. Results: The highest density of CD8+ lymphocytes was observed in plurihormonal PIT-1-positive tumors [17.61 cells\/mm2 (IQR: 17.61\u201360.36)], followed by somatotroph [13.2 (6.6\u201315.72)] and mammosomatotroph [13.83 (0\u201321.38)] tumors. A difference in CD8+ density was found between PIT-1-positive and PIT-1-negative tumors (n1 = 34, n2 = 6, U = 49.5, pexact = 0.050, r = 0.33); the medium effect size indicates a possible lineage-related trend. Another difference was observed between SF-1-positive and SF-1-negative tumors (p = 0.025), with SF-1 lineage tumors showing the lowest infiltration. No correlations were found between CD8+ density and tumor size, Knosp grade, or Ki-67 index. Conclusions: The distribution of intratumoral CD8+ T lymphocytes in PitNETs is highly heterogeneous and appears to be strongly dictated by the transcription factor-defined tumor lineage rather than by traditional clinicopathological markers of aggressiveness. PIT-1 lineage tumors harbor a more active immune microenvironment, while SF-1 lineage tumors are relatively \u2018immune-poor\u2019. These findings highlight the immunological diversity of PitNETs and support further investigation of the tumor immune landscape. Collaborative multi-institutional studies are required to validate these trends.<\/jats:p>","DOI":"10.3390\/cells15121115","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"1115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD8+ T Lymphocytes in Pituitary Neuroendocrine Tumors: Friend or Foe?"],"prefix":"10.3390","volume":"15","author":[{"given":"Valeria-Nicoleta","family":"Nastase","sequence":"first","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0067-8247","authenticated-orcid":false,"given":"Amalia Raluca","family":"Ceausu","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iulia Florentina","family":"Burcea","sequence":"additional","affiliation":[{"name":"\u201cC. I. Parhon\u201d National Institute of Endocrinology, 011683 Bucharest, Romania"},{"name":"Endocrinology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4568-2714","authenticated-orcid":false,"given":"Roxana Ioana","family":"Dumitriu-Stan","sequence":"additional","affiliation":[{"name":"\u201cC. I. Parhon\u201d National Institute of Endocrinology, 011683 Bucharest, Romania"},{"name":"Endocrinology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pusa Nela","family":"Gaje","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5755-179X","authenticated-orcid":false,"given":"Flavia","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Municipal Emergency Hospital, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Raica","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\/Histology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Angiogenesis Research Centre, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-5104","authenticated-orcid":false,"given":"Oana","family":"Albai","sequence":"additional","affiliation":[{"name":"Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Department of Diabetes, Nutrition and Metabolic Diseases Clinic, \u201cPius Br\u00eenzeu\u201d Emergency Clinical County University Hospital, 300723 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease\/MOL-NEPHRO-VASC, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Poiana","sequence":"additional","affiliation":[{"name":"\u201cC. I. Parhon\u201d National Institute of Endocrinology, 011683 Bucharest, Romania"},{"name":"Endocrinology Department, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0993-6206","authenticated-orcid":false,"given":"Bogdan","family":"Timar","sequence":"additional","affiliation":[{"name":"Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Department of Diabetes, Nutrition and Metabolic Diseases Clinic, \u201cPius Br\u00eenzeu\u201d Emergency Clinical County University Hospital, 300723 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease\/MOL-NEPHRO-VASC, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1056\/NEJMra1810772","article-title":"Pituitary-Tumor Endocrinopathies","volume":"382","author":"Melmed","year":"2020","journal-title":"N. 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