{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:35:07Z","timestamp":1790656507045,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["Medical Research Grant (Pfizer s.r.l: 55007559)"],"award-info":[{"award-number":["Medical Research Grant (Pfizer s.r.l: 55007559)"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Somatotropinomas are pituitary tumors with a heterogenous clinical behavior. The tumor microenvironment regulates the interaction between tumor cells and the host immune system, potentially modulating tumor behavior. Here, we aimed to investigate the tumor immune infiltration in a cohort of medically na\u00efve acromegaly patients. A retrospective, monocenter study was designed to analyze the presence of CD3+, CD20+, CD138+, CD4+, CD8+, CD68+ immune cells in samples of somatotropinomas and their prognostic significance on tumor behavior and response to first generation somatostatin analogs (fg\u2010SSA). Thirty\u2010six patients (23 females) were included in the study. Macroadenomas were identified in 23 cases: 12 with cavernous sinus invasion. The number of CD8+ lymphocytes positively correlated with CD4+ lymphocytes (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.05, r:0.245) and with CD68+ macrophages (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.01,\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.291). The CD8+\/CD4+ ratio inversely correlated with CD68+\/CD8+ ratio (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001,\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u22120.626). CD68+ macrophages positively correlated with tumor size (maximum diameter\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.003,\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.574; volume\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.009,\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.566) and were more numerous in somatotropinomas with Ki\u201067\u2009&gt;\u20093% (median 65\/HPF, IQR:15), compared to cases with Ki67\u2009&lt;\u20093% (median 50\/HPF, IQR:22,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001). CD8+ and CD138+ lymphocytes were more numerous in cases responsive to fg\u2010SSA (respectively median 18\/HPF IQR:18 and median 8\/HPF IQR: 6.5) as compared to fg\u2010SSA nonresponsive cases (median 14.5\/HPF IQR:40\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.03; median 3.5\/HPF IQR: 14\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.03). CD8+ lymphocytes act as single predictor of response to fg\u2010SSA, independently from age, GH and IGF\u2010I levels, tumor dimension and invasion. Our results support that lymphocytes and macrophages generate an immune network in somatotropinomas and the characteristic of the immune infiltrate may predict treatment outcome.\n                  <\/jats:p>","DOI":"10.1111\/jne.13263","type":"journal-article","created":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T15:44:00Z","timestamp":1679759040000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>CD68<\/scp>\n                    + and\n                    <scp>CD8<\/scp>\n                    + immune cells are associated with the growth pattern of somatotroph tumors and response to first generation somatostatin analogs"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-2392","authenticated-orcid":false,"given":"Sabrina","family":"Chiloiro","sequence":"first","affiliation":[{"name":"UOC Endocrinology and Diabetology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Department of Translational Medicine and Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Giampietro","sequence":"additional","affiliation":[{"name":"UOC Endocrinology and Diabetology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Department of Translational Medicine and Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Gessi","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liverana","family":"Lauretti","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"},{"name":"Department of Ageing, Neurosciences Head Neck and Orthopedics Sciences Catholic University of Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-9096","authenticated-orcid":false,"given":"Pier Paolo","family":"Mattogno","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"},{"name":"Department of Ageing, Neurosciences Head Neck and Orthopedics Sciences Catholic University of Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Cerroni","sequence":"additional","affiliation":[{"name":"UOC Endocrinology and Diabetology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Carlino","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quintino Giorgio","family":"De Alessandris","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"},{"name":"Department of Ageing, Neurosciences Head Neck and Orthopedics Sciences Catholic University of Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Olivi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"},{"name":"Department of Ageing, Neurosciences Head Neck and Orthopedics Sciences Catholic University of Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-4404","authenticated-orcid":false,"given":"Guido","family":"Rindi","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit Fondazione Policlinico Universitario A. Gemelli\u2014IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Pontecorvi","sequence":"additional","affiliation":[{"name":"UOC Endocrinology and Diabetology Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Department of Translational Medicine and Surgery Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"De Marinis","sequence":"additional","affiliation":[{"name":"UOC Endocrinology and Diabetology Fondazione Policlinico Universitario A. 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