{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:37:53Z","timestamp":1762299473441,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Octreotide long-acting repeatable (LAR) is largely used to treat functional and\/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to bind somatostatin receptors (SSTRs) on the tumour and metastasis, regulating growth hormone secretion and cell growth. Notably, SSTRs are also expressed, at different levels, on Tregs. Tregs, together with myeloid-derived suppressor cells (MDSCs), are key components in the anti-tumour immunoregulation. This is the first prospective study aimed to explore the impact of Octreotide (OCT) LAR on the immune system, with a particular focus on Tregs and MDSC cells. Here, we show that circulating Tregs are elevated in NENs patients compared to healthy donors and that treatment with OCT LAR significantly decrease the level of total Tregs and of the three functional Tregs populations: nTregs, eTregs and non-Tregs. Furthermore, OCT LAR treatment induces a functional impairment of the remaining circulating Tregs, significantly decreasing the expression of PD1, CTLA4 and ENTPD1. A trend in circulating MDSC cells is reported in patients treated with OCT LAR. The results reported here suggest that the effect of OCT LAR on Tregs could tip the balance of the patients\u2019 immune-system towards a durable anti-tumour immunosurveillance with consequent long-term control of the NENs disease.<\/jats:p>","DOI":"10.3390\/cancers12092422","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:56:58Z","timestamp":1598435818000},"page":"2422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of Octreotide Long-Acting Release on Tregs and MDSC Cells in Neuroendocrine Tumour Patients: A Pivotal Prospective Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6078-4271","authenticated-orcid":false,"given":"Claudia","family":"von Arx","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Thoracic oncology Istituto Nazionale Tumori, IRCCS Fondazione G.Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5420-395X","authenticated-orcid":false,"given":"Giuseppina","family":"Rea","sequence":"additional","affiliation":[{"name":"UOC Bersagli Molecolari del Microambiente, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Napolitano","sequence":"additional","affiliation":[{"name":"UOC Bersagli Molecolari del Microambiente, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-3855","authenticated-orcid":false,"given":"Alessandro","family":"Ottaiano","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9943-6079","authenticated-orcid":false,"given":"Fabiana","family":"Tatangelo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Istituto Nazionale Tumori, IRCCS-Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3093-5408","authenticated-orcid":false,"given":"Francesco","family":"Izzo","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-5370","authenticated-orcid":false,"given":"Antonella","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Radiant and Metabolic Therapy, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ottavia","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department of Abdominal Oncology, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Di Sarno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, AORN dei Colli, Ospedale \u201cA. Monaldi\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Botti","sequence":"additional","affiliation":[{"name":"Scientific Directorate, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Scala","sequence":"additional","affiliation":[{"name":"UOC Bersagli Molecolari del Microambiente, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-354X","authenticated-orcid":false,"given":"Salvatore","family":"Tafuto","sequence":"additional","affiliation":[{"name":"Sarcomas and Rare Tumours Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.neo.2017.09.002","article-title":"Nothing but NET: A Review of Neuroendocrine Tumors and Carcinomas","volume":"19","author":"Oronsky","year":"2017","journal-title":"Neoplasia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","article-title":"Trends in the Incidence, Prevalence, and Survival Outcomes in Patients with Neuroendocrine Tumors in the United States","volume":"3","author":"Dasari","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1677\/ERC-07-0288","article-title":"Somatostatin analogues in the control of neuroendocrine tumours: Efficacy and mechanisms","volume":"15","author":"Shimon","year":"2008","journal-title":"Endocr. 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