{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:12:04Z","timestamp":1793146324520,"version":"4.5.0"},"reference-count":53,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNSW University Postgraduate Award","award":["RSRE7050"],"award-info":[{"award-number":["RSRE7050"]}]},{"name":"Garvan Support Award Allowance"},{"name":"NHMRC Investigator Grant","award":["GNT2009840"],"award-info":[{"award-number":["GNT2009840"]}]},{"name":"Ipsen Research Grant"},{"name":"Novartis Research Grant"},{"name":"Curran Foundation Research Grant"},{"name":"St Vincent\u2019s Clinic Research Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>There is an ongoing need to identify prognostic and therapeutic biomarkers and develop alternative treatment options to treat aggressive and metastatic pituitary neuroendocrine tumors (PitNETs). This study aimed to examine the pituitary tumor immune microenvironment and correlate this with tumor behavior to identify novel biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective study of patients who underwent surgical resection of aggressive and nonaggressive PitNETs. Immune cells, immune checkpoints, and markers of cell cycle regulation and senescence were analyzed using immunohistochemistry. Cytokines and chemokines were analyzed using a multiplex immunoassay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 48 PitNET samples were included in the study; 12 were classified as aggressive PitNETs (APT) and 3 patients died from pituitary disease. APTs compared with non-APTs had higher CD3 T lymphocyte and CD163 macrophage infiltrate as well as lower expression of interferon gamma (IFN-\u03b3) and platelet-derived growth factor-AA (PDGF-AA). On analysis of tumor types, this was also observed in aggressive Pit1 PitNETs compared with SF1 PitNETs. Compared with SF1 PitNETs, both aggressive and nonaggressive Pit1 PitNETs exhibited increased expression of checkpoint marker programmed death-ligand 1 (PD-L1) and senescence markers p16 and p21. Pit1 and TPit PitNETs were more likely to demonstrate a perivascular pattern of immune cell infiltrate than SF1 PitNETs. Monokine induced by gamma interferon (MIG), macrophage inflammatory protein 1 beta (MIP1\u03b2), and interleukin-1 receptor antagonist (IL1RA) positively correlated with T lymphocytes, dendritic cells, and CD163 macrophages. Increased CD163 was associated with tumor recurrence, and increased interleukin-8 (IL-8) and transforming growth factor beta (TGF\u03b2) was associated with death from pituitary disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Aggressive PitNETs display a distinct tumor microenvironment characterized by increased immune cell infiltrate. These findings may offer novel prognostic biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag306","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:11:02Z","timestamp":1785323462000},"source":"Crossref","is-referenced-by-count":1,"title":["Aggressive pituitary neuroendocrine tumors display a distinct immune microenvironment"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7404-6464","authenticated-orcid":false,"given":"Lydia S","family":"Lamb","sequence":"first","affiliation":[{"name":"Neuroendocrine Research Program, St Vincent's Centre for Applied Medical Research , Sydney, NSW 2010 , Australia"},{"name":"School of Clinical Medicine, UNSW Australia , Sydney, NSW 2052 , 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