ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1579948
This article is part of the Research TopicPrecision Therapeutics in Rare Cancers: Targeting Tumor Microenvironment and Biomarker-Driven ApproachesView all 3 articles
Immune profiling of pediatric germ cell tumors identifies key cell populations and novel therapeutic targets
Provisionally accepted
Lenilson Silva1,2
Ingridy Izabella Vieira Cardoso1,2Marcelo Cavalcanti da Cruz3Thaíssa Maria Veiga Faria4Gisele Eiras Martins4Bruna Minniti Mançano4Luiz Fernando Lopes2,4,5Rui Manuel Reis1,6
Daniel Antunes Moreno1
Mariana Tomazini Pinto1,2*- 1Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
- 2Pediatric Oncology Research Group (GPOPed). Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
- 3Department of Pathology, Barretos Cancer Hospital, Barretos, Brazil
- 4Barretos Children’s Cancer Hospital, Barretos, Brazil
- 5Molecular Oncology Research Center, Barretos Cancer Hospital, Sao Paulo, Sao Paulo, Brazil
- 6Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Braga, Portugal
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Introduction: 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. Methods: 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). Results: Immune profiling revealed distinct immune microenvironments across the GCT subtypes. Dysgerminomas exhibited an immune-active profile with elevated levels of T cells, CD8 + T cells, and cytotoxic cells, alongside upregulation of immune checkpoints CTLA4, TIGIT, and IDO1, suggesting potential responsiveness to checkpoint inhibitors. In contrast, yolk sac tumors displayed an immunosuppressive environment with high CD24 and PVR expression, indicative of unique immune evasion mechanisms. Embryonal carcinomas also showed high CD24 expression. An in silico analysis of adult GCTs highlighted similarities and differences with pediatric cases; IDO1 and CD24 were consistently upregulated across age groups, while CTLA4 and PVR showed variation. Conclusion: 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.
Keywords: germ cell tumors, pediatric tumor, Immune profiling, Immune checkpoint, tumor immunology
Received: 19 Feb 2025; Accepted: 05 May 2025.
Copyright: © 2025 Silva, Izabella Vieira Cardoso, Cavalcanti da Cruz, Maria Veiga Faria, Eiras Martins, Minniti Mançano, Fernando Lopes, Manuel Reis, Moreno and Tomazini Pinto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mariana Tomazini Pinto, Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
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