{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:25:13Z","timestamp":1793157913681,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"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>Background: Aggressive and metastatic PitNETs are challenging conditions. Immune checkpoint inhibitors (ICIs) are currently considered in cases resistant to temozolomide (TMZ). However, clinical experience is essentially limited to case reports, with variable outcomes. Material and\u00a0Methods: The effects of ICIs on 12 aggressive\/metastatic PitNETs from the literature were reviewed and analyzed according to tumor characteristics, with the additional description of a silent-Pit1 metastatic tumor responding to pembrolizumab. Results: Most cases were metastatic (10\/13: 6 corticotroph, 3 lactotroph, 1 silent Pit1); 3 were aggressive (2 corticotroph, 1 lactotroph). ICIS was used either as monotherapy or in combination. At last follow-up on ICI, a complete response (CR) was present in 3 cases and a partial response (PR) in 2 cases (4\/5 metastatic). One sustained stable disease (SD) was reported. Progressive disease (PD) was observed in 7 cases, 3 of them after initial SD (n = 1) or PR (n = 3), with 2 reported deaths. PDL1 expression was studied in 10 cases and was high (&gt;95%) in 2 Pit1-derived metastatic PitNETs (1 CR and 1 remarkable PR) but absent\/low (&lt;1%) in the remaining cases (including 1 CP and 2 PR). Elevated tumor mutation burden could be informative in corticotroph PitNETs, especially in mismatch repair-deficient tumors. Conclusion: Significant benefits from ICIs were documented in about half of TMZ-resistant PitNETS. High PDL1 expression was associated with remarkable responses but may be dispensable. Based on their acceptable tolerance and awaiting recognized predictors of response, ICIs may be considered a valuable option for such patients.<\/jats:p>","DOI":"10.3390\/cancers14174093","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T21:03:51Z","timestamp":1661375031000},"page":"4093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Immunotherapy for Aggressive and Metastatic Pituitary Neuroendocrine Tumors (PitNETs): State-of-the Art"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1066-0064","authenticated-orcid":false,"given":"Tiziana","family":"Feola","sequence":"first","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Experimental Medicine, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4710-9877","authenticated-orcid":false,"given":"Francesca","family":"Carbonara","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Verrico","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Di Crescenzo","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6223-9952","authenticated-orcid":false,"given":"Francesca","family":"Gianno","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Radiological, Oncological and Pathological Sciences, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Colonnese","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-8282","authenticated-orcid":false,"given":"Antonietta","family":"Arcella","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"de Alcubierre","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silverio","family":"Tomao","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Esposito","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Neurology and Psychiatry, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-2380","authenticated-orcid":false,"given":"Felice","family":"Giangaspero","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Radiological, Oncological and Pathological Sciences, La Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1239-1603","authenticated-orcid":false,"given":"Giuseppe","family":"Minniti","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-8997","authenticated-orcid":false,"given":"Marie-Lise","family":"Jaffrain-Rea","sequence":"additional","affiliation":[{"name":"Neuromed IRCCS, 86077 Pozzilli, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41574-021-00550-w","article-title":"Aggressive Pituitary Tumours and Pituitary Carcinomas","volume":"17","author":"Raverot","year":"2021","journal-title":"Nat. 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