{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:05:00Z","timestamp":1790071500991,"version":"4.0.1"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Background: Glioblastoma (GBM) represents the most aggressive and lethal primary malignancy of the central nervous system in adults. Although clinical trials evaluating immunotherapy strategies have increased substantially in recent years, the available evidence remains highly fragmented. This scoping review aimed to synthesize the available evidence from clinical trials investigating immunotherapy for newly diagnosed GBM. Methods: PubMed, Scopus, Embase, and Web of Science were searched from inception to July 2026 for clinical trials of first-line immunotherapy in adults with newly diagnosed GBM; recurrent, mixed-setting, preclinical, and abstract-only reports were excluded. Outcomes were overall survival (OS) and progression-free survival (PFS), adverse events, and treatment-related deaths. Results: Six therapeutic classes were represented: immune checkpoint inhibitors (13 reports), peptide and neoantigen vaccines (12), dendritic cell vaccines (10), adoptive cell therapies (5), oncolytic viral and gene therapies (3), and autologous formalin-fixed tumor vaccines (2). The evidence base was predominantly early-phase: 36 of 45 studies enrolled fewer than 100 patients, only 14 included a randomized comparison, and 5 were phase III. Median OS ranged from 11.5 to 38.4 months and median PFS from 1.3 to 60.1 months, the highest estimates arising from small, highly selected single-arm cohorts. No randomized trial improved OS. Important adverse events were rare and almost exclusively confined to checkpoint inhibitor trials. Conclusions: Immunotherapy in newly diagnosed GBM is feasible and tolerable but has not improved survival, with outcomes still determined more by MGMT promoter status and extent of resection than by treatment assignment. Biomarker-enriched selection, lymphocyte-sparing design and rational combinations are required in future trials.<\/jats:p>","DOI":"10.3390\/jpm16090479","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:04:17Z","timestamp":1790067857000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunotherapy for Newly Diagnosed Glioblastoma: Current Evidence and Future Perspectives"],"prefix":"10.3390","volume":"16","author":[{"given":"Rudolfh Batista","family":"Arend","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Federal University of Fronteira Sul, Passo Fundo 99010-200, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-9481","authenticated-orcid":false,"given":"Bruno Zilli","family":"Peroni","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Federal University of Fronteira Sul, Passo Fundo 99010-200, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7595-7082","authenticated-orcid":false,"given":"Natan Lucca","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Federal University of Santa Catarina, Ararangu\u00e1 99010-200, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8253-3272","authenticated-orcid":false,"given":"Miguel","family":"Cruz Garcia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Medical Education, Rio de Janeiro 20071-004, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4104-9526","authenticated-orcid":false,"given":"Amanda Hedel","family":"Koerich","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Passo Fundo, Passo Fundo 99052-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Felipe","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Federal University of Fronteira Sul, Passo Fundo 99010-200, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Torres Fonseca","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Institute of Medical Education, Rio de Janeiro 20071-004, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2619-3246","authenticated-orcid":false,"given":"Kelvin","family":"Tapia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad Adventista del Plata (UAP), Libertador San Mart\u00edn E3103XAF, Entre R\u00edos, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kerpel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Federal University of Santa Maria, Santa Maria 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2538-9599","authenticated-orcid":false,"given":"Gustavo Simiano","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Neurological Institute of Curitiba, Curitiba 82821-020, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Roman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Federal University of Fronteira Sul, Passo Fundo 99010-200, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-4800","authenticated-orcid":false,"given":"Guilherme","family":"Gago","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Universit\u00e9 Laval,  Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7261-7216","authenticated-orcid":false,"given":"Martin Batista Coutinho","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Passo Fundo, Passo Fundo 99052-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Delacy Martini","family":"Vial","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Irmandade Santa Casa de Miseric\u00f3rdia de Porto Alegre, Hospital S\u00e3o Jos\u00e9, Porto Alegre 90040-020, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-5000","authenticated-orcid":false,"given":"Edoardo","family":"Agosti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Division of Neurosurgery, Radiological Sciences and Public Health, University of Brescia, Lombardy, 25121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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