{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:15:41Z","timestamp":1784132141572,"version":"3.55.0"},"reference-count":67,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (HG-NENs) comprise both highly proliferating well-differentiated NENs, called grade 3 neuroendocrine (NE) tumors, and poorly differentiated NENs (also named neuroendocrine carcinomas). The clinical management of these neoplasms poses unique challenges, and, while platinum plus etoposide is the first-line therapy in advanced setting of neuroendocrine carcinomas, this is not the optimal regimen in G3 neuroendocrine tumors in which other chemotherapy schemes, targeted agents, and somatostatin analogs have shown to be active. However, overall response rates and clinical benefit are not satisfactory. Interestingly, HG-NENs may be a more suitable target for immune checkpoints inhibitors (ICIs) than low-grade NENs, because of their higher tumor mutational burden, increased PD-1 expression, probable increased PD-L1 expression, and higher immune infiltration of tumor microenvironment. With these assumptions, few clinical trials have investigated the efficacy and safety of ICIs in HG-NEN. With our work, we aimed to provide a comprehensive overview of the available literature data about ICIs' role in HG GEP NENs, by analyzing the critical points regarding study population, study design, study results, and potential useful biomarkers for selecting HG-GEP-NEN patients for ICI therapy.<\/jats:p>","DOI":"10.1210\/endrev\/bnaf037","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:10:55Z","timestamp":1759925455000},"page":"178-190","source":"Crossref","is-referenced-by-count":2,"title":["Immune Checkpoint Inhibitors in High-grade Gastroenteropancreatic Neuroendocrine Neoplasms"],"prefix":"10.1210","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-0704","authenticated-orcid":false,"given":"Nicola","family":"Fazio","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS , Milan 20141 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-8657","authenticated-orcid":false,"given":"Anna","family":"La Salvia","sequence":"additional","affiliation":[{"name":"National Center for Drug Research and Evaluation, National Institute of Health (Istituto Superiore Di Sanit\u00e0) , Rome 00161 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"issue":"1","key":"2026031022482058500_bnaf037-B1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s12022-020-09660-z","article-title":"Genomics of high-grade neuroendocrine neoplasms: well-differentiated neuroendocrine tumor with high-grade features (G3 NET) and neuroendocrine carcinomas (NEC) of various anatomic sites","volume":"32","author":"Uccella","year":"2021","journal-title":"Endocr Pathol"},{"issue":"1","key":"2026031022482058500_bnaf037-B2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000493318","article-title":"Unmet needs in high-grade gastroenteropancreatic neuroendocrine neoplasms (WHO G3)","volume":"108","author":"Sorbye","year":"2019","journal-title":"Neuroendocrinology"},{"issue":"7","key":"2026031022482058500_bnaf037-B3","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.annonc.2020.03.304","article-title":"Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Pavel","year":"2020","journal-title":"Ann Oncol"},{"issue":"1","key":"2026031022482058500_bnaf037-B4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1159\/000445165","article-title":"The clinicopathologic heterogeneity of grade 3 gastroenteropancreatic neuroendocrine neoplasms: morphological differentiation and proliferation identify different prognostic categories","volume":"104","author":"Milione","year":"2017","journal-title":"Neuroendocrinology"},{"issue":"1","key":"2026031022482058500_bnaf037-B5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/ERC-21-0152","article-title":"The molecular characteristics of high-grade gastroenteropancreatic neuroendocrine neoplasms","volume":"29","author":"Venizelos","year":"2021","journal-title":"Endocr Relat Cancer"},{"issue":"4","key":"2026031022482058500_bnaf037-B6","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1530\/ERC-15-0119","article-title":"Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms","volume":"22","author":"Heetfeld","year":"2015","journal-title":"Endocr Relat Cancer"},{"issue":"18","key":"2026031022482058500_bnaf037-B7","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1002\/cncr.28721","article-title":"Gastroenteropancreatic high-grade neuroendocrine carcinoma","volume":"120","author":"Sorbye","year":"2014","journal-title":"Cancer"},{"issue":"2","key":"2026031022482058500_bnaf037-B8","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3390\/jcm12020717","article-title":"Chemotherapy in well differentiated neuroendocrine tumors (NET) G1, G2, and G3: a narrative review","volume":"12","author":"Zappi","year":"2023","journal-title":"J Clin Med"},{"issue":"12","key":"2026031022482058500_bnaf037-B9","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"},{"issue":"1","key":"2026031022482058500_bnaf037-B10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41392-023-01522-4","article-title":"Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"Suppl 5","key":"2026031022482058500_bnaf037-B11","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1053\/j.seminoncol.2014.09.004","article-title":"Mechanism of action of immunotherapy","volume":"41","author":"Disis","year":"2014","journal-title":"Semin Oncol"},{"issue":"3","key":"2026031022482058500_bnaf037-B12","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s10555-023-10121-2","article-title":"Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma","volume":"42","author":"Ooki","year":"2023","journal-title":"Cancer Metastasis Rev"},{"issue":"8","key":"2026031022482058500_bnaf037-B13","doi-asserted-by":"crossref","first-page":"e3004","DOI":"10.1038\/cddis.2017.401","article-title":"Role of PD-L1 expression as a biomarker for GEP neuroendocrine neoplasm grading","volume":"8","author":"Cavalcanti","year":"2017","journal-title":"Cell Death Dis"},{"issue":"3","key":"2026031022482058500_bnaf037-B14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1530\/ERC-18-0494","article-title":"Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia","volume":"26","author":"B\u00f6sch","year":"2019","journal-title":"Endocr Relat Cancer"},{"issue":"12","key":"2026031022482058500_bnaf037-B15","doi-asserted-by":"crossref","first-page":"e0243900","DOI":"10.1371\/journal.pone.0243900","article-title":"PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3","volume":"15","author":"Ali","year":"2020","journal-title":"PLoS One"},{"issue":"4","key":"2026031022482058500_bnaf037-B16","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1158\/1078-0432.CCR-14-1860","article-title":"Immune escape mechanisms as a guide for cancer immunotherapy","volume":"21","author":"Beatty","year":"2015","journal-title":"Clin Cancer Res"},{"issue":"2","key":"2026031022482058500_bnaf037-B17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000497355","article-title":"The tumor microenvironment in neuroendocrine tumors: biology and therapeutic implications","volume":"109","author":"Cives","year":"2019","journal-title":"Neuroendocrinology"},{"issue":"2","key":"2026031022482058500_bnaf037-B18","doi-asserted-by":"crossref","first-page":"188311","DOI":"10.1016\/j.bbcan.2019.188311","article-title":"The tumor immune microenvironment in gastroenteropancreatic neuroendocrine neoplasms","volume":"1872","author":"Zhang","year":"2019","journal-title":"Biochim Biophys Acta Rev Cancer"},{"issue":"1","key":"2026031022482058500_bnaf037-B19","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1038\/s41467-021-24812-3","article-title":"The genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets","volume":"12","author":"Van Riet","year":"2021","journal-title":"Nat Commun"},{"issue":"7643","key":"2026031022482058500_bnaf037-B20","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nature21063","article-title":"Whole-genome landscape of pancreatic neuroendocrine tumours","volume":"543","author":"Scarpa","year":"2017","journal-title":"Nature"},{"key":"2026031022482058500_bnaf037-B21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ejca.2022.03.029","article-title":"Avelumab in unresectable\/metastatic, progressive, grade 2\u20133 neuroendocrine neoplasms (NENs): combined results from NET-001 and NET-002 trials","volume":"169","author":"Chan","year":"2022","journal-title":"Eur J Cancer"},{"issue":"9","key":"2026031022482058500_bnaf037-B22","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1038\/s41416-020-0775-0","article-title":"Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials","volume":"122","author":"Vijayvergia","year":"2020","journal-title":"Br J Cancer"},{"issue":"3","key":"2026031022482058500_bnaf037-B23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1530\/ERC-20-0382","article-title":"Spartalizumab in metastatic, well\/poorly-differentiated neuroendocrine neoplasms","volume":"28","author":"Yao","year":"2021","journal-title":"Endocr Relat Cancer"},{"issue":"10","key":"2026031022482058500_bnaf037-B24","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1158\/1078-0432.CCR-19-4000","article-title":"Efficacy, safety, and biomarkers of Toripalimab in patients with recurrent or metastatic neuroendocrine neoplasms: a multiple-center phase ib trial","volume":"26","author":"Lu","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"10","key":"2026031022482058500_bnaf037-B25","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1158\/1078-0432.CCR-19-3356","article-title":"A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART SWOG 1609) in patients with nonpancreatic neuroendocrine tumors","volume":"26","author":"Patel","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"17","key":"2026031022482058500_bnaf037-B26","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.1002\/cncr.33591","article-title":"A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: high-grade neuroendocrine neoplasm cohort","volume":"127","author":"Patel","year":"2021","journal-title":"Cancer"},{"issue":"17","key":"2026031022482058500_bnaf037-B27","doi-asserted-by":"crossref","first-page":"4454","DOI":"10.1158\/1078-0432.CCR-20-0621","article-title":"Immunotherapy of ipilimumab and nivolumab in patients with advanced neuroendocrine tumors: a subgroup analysis of the CA209-538 clinical trial for rare cancers","volume":"26","author":"Klein","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"1","key":"2026031022482058500_bnaf037-B28","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1038\/s41467-023-38611-5","article-title":"Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin","volume":"14","author":"Capdevila","year":"2023","journal-title":"Nat Commun"},{"issue":"1","key":"2026031022482058500_bnaf037-B29","doi-asserted-by":"crossref","first-page":"6753","DOI":"10.1038\/s41467-024-50969-8","article-title":"Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 neuroendocrine neoplasms of gastroenteropancreatic or unknown origin: the multicenter phase 2 NICE-NEC trial (GETNE-T1913)","volume":"15","author":"Riesco-Martinez","year":"2024","journal-title":"Nat Commun"},{"issue":"4","key":"2026031022482058500_bnaf037-B30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1158\/1078-0432.CCR-22-1552","article-title":"A phase II clinical trial of nivolumab and temozolomide for neuroendocrine neoplasms","volume":"29","author":"Owen","year":"2023","journal-title":"Clin Cancer Res"},{"issue":"4","key":"2026031022482058500_bnaf037-B31","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/cncr.31124","article-title":"Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: a SEER database analysis of 162,983 cases","volume":"124","author":"Dasari","year":"2018","journal-title":"Cancer"},{"key":"2026031022482058500_bnaf037-B32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pharmthera.2017.06.002","article-title":"Treatment advances in small cell lung cancer (SCLC)","volume":"180","author":"Waqar","year":"2017","journal-title":"Pharmacol Ther"},{"issue":"23","key":"2026031022482058500_bnaf037-B33","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa1809064","article-title":"First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer","volume":"379","author":"Horn","year":"2018","journal-title":"N Engl J Med"},{"issue":"10212","key":"2026031022482058500_bnaf037-B34","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(19)32222-6","article-title":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial","volume":"394","author":"Paz-Ares","year":"2019","journal-title":"Lancet"},{"issue":"21","key":"2026031022482058500_bnaf037-B35","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1200\/JCO.20.00793","article-title":"Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study","volume":"38","author":"Rudin","year":"2020","journal-title":"J Clin Oncol"},{"issue":"16","key":"2026031022482058500_bnaf037-B36","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1016\/j.ejca.2015.06.131","article-title":"Diagnosis and treatment of Merkel cell carcinoma. European consensus-based interdisciplinary guideline","volume":"51","author":"Lebbe","year":"2015","journal-title":"Eur J Cancer"},{"issue":"11","key":"2026031022482058500_bnaf037-B37","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1245\/s10434-016-5266-4","article-title":"Analysis of prognostic factors from 9387 Merkel cell carcinoma cases forms the basis for the new 8th edition AJCC staging system","volume":"23","author":"Harms","year":"2016","journal-title":"Ann Surg Oncol"},{"issue":"26","key":"2026031022482058500_bnaf037-B38","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa1603702","article-title":"PD-1 blockade with Pembrolizumab in advanced Merkel-cell carcinoma","volume":"374","author":"Nghiem","year":"2016","journal-title":"N Engl J Med"},{"issue":"7","key":"2026031022482058500_bnaf037-B39","doi-asserted-by":"crossref","first-page":"e002646","DOI":"10.1136\/jitc-2021-002646","article-title":"First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study","volume":"9","author":"D'Angelo","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"22","key":"2026031022482058500_bnaf037-B40","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1200\/JCO.20.00201","article-title":"Neoadjuvant nivolumab for patients with resectable Merkel cell carcinoma in the CheckMate 358 trial","volume":"38","author":"Topalian","year":"2020","journal-title":"J Clin Oncol"},{"issue":"4","key":"2026031022482058500_bnaf037-B41","doi-asserted-by":"crossref","first-page":"e002478","DOI":"10.1136\/jitc-2021-002478","article-title":"Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma","volume":"9","author":"Nghiem","year":"2021","journal-title":"J Immunother Cancer"},{"issue":"5","key":"2026031022482058500_bnaf037-B42","doi-asserted-by":"crossref","first-page":"102977","DOI":"10.1016\/j.esmoop.2024.102977","article-title":"Merkel-cell carcinoma: ESMO-EURACAN clinical practice guideline for diagnosis, treatment and follow-up","volume":"9","author":"Lugowska","year":"2024","journal-title":"ESMO Open"},{"issue":"1","key":"2026031022482058500_bnaf037-B43","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1186\/s12885-024-13129-1","article-title":"Efficacy and safety of PD-1\/PD-L1 inhibitors in patients with Merkel cell carcinoma: a systematic review and meta-analysis","volume":"24","author":"de Moraes","year":"2024","journal-title":"BMC Cancer"},{"issue":"2","key":"2026031022482058500_bnaf037-B44","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41416-023-02298-8","article-title":"Pembrolizumab alone and pembrolizumab plus chemotherapy in previously treated, extrapulmonary poorly differentiated neuroendocrine carcinomas","volume":"129","author":"Raj","year":"2023","journal-title":"Br J Cancer"},{"key":"2026031022482058500_bnaf037-B45","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejca.2023.03.024","article-title":"Molecular profiling and target actionability for precision medicine in neuroendocrine neoplasms: real-world data","volume":"186","author":"Boileve","year":"2023","journal-title":"Eur J Cancer"},{"issue":"suppl_2","key":"2026031022482058500_bnaf037-B46","doi-asserted-by":"crossref","first-page":"S498","DOI":"10.1016\/j.annonc.2023.09.670","article-title":"Cabozantinib plus atezolizumab in advanced and progressive neoplasms of the endocrine system: a multi-cohort basket phase II trial (CABATEN\/GETNE-T1914)","volume":"34","author":"Capdevila Castillon","year":"2023","journal-title":"Ann Oncol"},{"issue":"12","key":"2026031022482058500_bnaf037-B47","doi-asserted-by":"crossref","first-page":"e542","DOI":"10.1016\/S1470-2045(16)30406-5","article-title":"Predictive biomarkers for checkpoint inhibitor-based immunotherapy","volume":"17","author":"Gibney","year":"2016","journal-title":"Lancet Oncol"},{"issue":"2","key":"2026031022482058500_bnaf037-B48","first-page":"283","article-title":"Towards the prediction of responses to cancer immunotherapy: a multi-omics review","volume":"15","author":"Tao","year":"2025","journal-title":"Life (Basel)"},{"issue":"3","key":"2026031022482058500_bnaf037-B49","doi-asserted-by":"crossref","first-page":"e13249","DOI":"10.1111\/jne.13249","article-title":"European neuroendocrine tumor society (ENETS) 2023 guidance paper for digestive neuroendocrine carcinoma","volume":"35","author":"Sorbye","year":"2023","journal-title":"J Neuroendocrinol"},{"issue":"12","key":"2026031022482058500_bnaf037-B50","doi-asserted-by":"crossref","first-page":"e13343","DOI":"10.1111\/jne.13343","article-title":"European neuroendocrine tumour society (ENETS) 2023cguidance paper for nonfunctioning pancreatic neuroendocrine tumours","volume":"35","author":"Kos-Kudla","year":"2023","journal-title":"J Neuroendocrinol"},{"issue":"9","key":"2026031022482058500_bnaf037-B51","doi-asserted-by":"crossref","first-page":"e13423","DOI":"10.1111\/jne.13423","article-title":"European neuroendocrine tumor society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours","volume":"36","author":"Lamarca","year":"2024","journal-title":"J Neuroendocrinol"},{"issue":"8","key":"2026031022482058500_bnaf037-B52","doi-asserted-by":"crossref","first-page":"e220206","DOI":"10.1530\/ERC-22-0206","article-title":"Expert consensus practice recommendations of the North American neuroendocrine tumor society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms","volume":"30","author":"Eads","year":"2023","journal-title":"Endocr Relat Cancer"},{"issue":"1","key":"2026031022482058500_bnaf037-B53","doi-asserted-by":"crossref","first-page":"1878599","DOI":"10.1080\/2162402X.2021.1878599","article-title":"Efficacy and safety of anti-PD-1\/PD-L1 combinations versus standard of care in cancer: a systematic review and meta-analysis","volume":"10","author":"Carretero-Gonz\u00e1lez","year":"2021","journal-title":"Oncoimmunology"},{"issue":"1","key":"2026031022482058500_bnaf037-B54","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jpainsymman.2019.03.015","article-title":"Patient-reported outcomes for cancer patients receiving checkpoint inhibitors: opportunities for palliative care\u2014a systematic review","volume":"58","author":"Hall","year":"2019","journal-title":"J Pain Symptom Manage"},{"issue":"1","key":"2026031022482058500_bnaf037-B55","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41572-020-0160-6","article-title":"Immune-related adverse events of checkpoint inhibitors","volume":"6","author":"Ramos-Casals","year":"2020","journal-title":"Nat Rev Dis Primers"},{"issue":"14","key":"2026031022482058500_bnaf037-B56","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N Engl J Med"},{"issue":"22","key":"2026031022482058500_bnaf037-B57","doi-asserted-by":"crossref","first-page":"5943","DOI":"10.1158\/1078-0432.CCR-20-1804","article-title":"Comprehensive genomic profiling of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs)","volume":"26","author":"Puccini","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"1","key":"2026031022482058500_bnaf037-B58","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1530\/ERC-14-0410","article-title":"Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity","volume":"22","author":"Sahnane","year":"2015","journal-title":"Endocr Relat Cancer"},{"issue":"S1","key":"2026031022482058500_bnaf037-B59","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s00292-021-00948-3","article-title":"MSI testing: what's new? What should be considered?","volume":"42","author":"R\u00fcschoff","year":"2021","journal-title":"Pathologe"},{"issue":"9","key":"2026031022482058500_bnaf037-B60","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.annonc.2022.05.519","article-title":"Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study","volume":"33","author":"Maio","year":"2022","journal-title":"Ann Oncol"},{"issue":"10","key":"2026031022482058500_bnaf037-B61","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S1470-2045(20)30445-9","article-title":"Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study","volume":"21","author":"Marabelle","year":"2020","journal-title":"Lancet Oncol"},{"issue":"1","key":"2026031022482058500_bnaf037-B62","doi-asserted-by":"crossref","first-page":"100364","DOI":"10.1016\/j.esmoop.2021.100364","article-title":"Efficacy of ipilimumab and nivolumab in patients with high-grade neuroendocrine neoplasms","volume":"7","author":"Al-Toubah","year":"2022","journal-title":"ESMO Open"},{"key":"2026031022482058500_bnaf037-B63","author":"De Mestier","year":"2025"},{"key":"2026031022482058500_bnaf037-B64","author":"La Salvia","year":"2021"},{"issue":"24","key":"2026031022482058500_bnaf037-B65","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.2217\/fon-2022-0196","article-title":"Phase I trial of the DLL3\/CD3 bispecific T-cell engager BI 764532 in DLL3-positive small-cell lung cancer and neuroendocrine carcinomas","volume":"18","author":"Wermke","year":"2022","journal-title":"Future Oncol"},{"issue":"2","key":"2026031022482058500_bnaf037-B66","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1158\/0008-5472.CAN-22-1433","article-title":"Immunotherapeutic targeting and PET imaging of DLL3 in small-cell neuroendocrine prostate cancer","volume":"83","author":"Chou","year":"2023","journal-title":"Cancer Res"},{"issue":"16","key":"2026031022482058500_bnaf037-B67","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.3390\/cancers14163991","article-title":"Immunotherapy of neuroendocrine neoplasms: any role for the chimeric antigen receptor T cells?","volume":"14","author":"Fanciulli","year":"2022","journal-title":"Cancers (Basel)"}],"container-title":["Endocrine Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/edrv\/advance-article-pdf\/doi\/10.1210\/endrev\/bnaf037\/64560327\/bnaf037.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/edrv\/article-pdf\/47\/2\/178\/64560327\/bnaf037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/edrv\/article-pdf\/47\/2\/178\/64560327\/bnaf037.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:48:34Z","timestamp":1773197314000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/edrv\/article\/47\/2\/178\/8277972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":67,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,10,9]]},"published-print":{"date-parts":[[2026,3,11]]}},"URL":"https:\/\/doi.org\/10.1210\/endrev\/bnaf037","relation":{},"ISSN":["0163-769X","1945-7189"],"issn-type":[{"value":"0163-769X","type":"print"},{"value":"1945-7189","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2025,10,9]]}}}