{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:38:05Z","timestamp":1774928285322,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Pediatric germ cell tumors (GCTs) are rare malignancies, comprising only about 3% of childhood cancers. Despite surgery and platinum-based chemotherapy being mainstays of treatment, their effectiveness varies by tumor subtype, and long-term toxicities remain a concern. We therefore explored the immune landscape of pediatric GCTs to uncover subtype-specific immunological features and identify potential immunotherapeutic targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective study investigated the immune landscape of pediatric GCTs, utilizing a cohort of 17 patients, including 14 extracranial GCTs (11 ovarian, 3 testicular), three central nervous system (CNS) mixed tumors and four non-neoplastic tissues (controls).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immune profiling revealed distinct immune microenvironments across the GCT subtypes. Dysgerminomas exhibited an immune-active profile with elevated levels of T cells, CD8<jats:sup>+<\/jats:sup> T cells, and cytotoxic cells, alongside upregulation of immune checkpoints <jats:italic>CTLA4<\/jats:italic>, <jats:italic>TIGIT<\/jats:italic>, and <jats:italic>IDO1<\/jats:italic>, suggesting potential responsiveness to checkpoint inhibitors. In contrast, yolk sac tumors displayed an immunosuppressive environment with high <jats:italic>CD24<\/jats:italic> and <jats:italic>PVR<\/jats:italic> expression, indicative of unique immune evasion mechanisms. Embryonal carcinomas also showed high <jats:italic>CD24<\/jats:italic> expression. An <jats:italic>in silico<\/jats:italic> analysis of adult GCTs highlighted similarities and differences with pediatric cases; <jats:italic>IDO1<\/jats:italic> and <jats:italic>CD24<\/jats:italic> were consistently upregulated across age groups, while <jats:italic>CTLA4<\/jats:italic> and <jats:italic>PVR<\/jats:italic> showed variation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, this study provides new insights into pediatric GCT immunology, supporting the potential for tailored immunotherapeutic strategies targeting the distinct immune profiles of pediatric GCT histologies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1579948","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:22:15Z","timestamp":1750396935000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune profiling of pediatric germ cell tumors identifies key cell 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