Immune profiling of pediatric germ cell tumors identifies key cell populations and novel therapeutic targets

Autor(es)

Silva, Lenilson ; Cardoso, Ingridy Izabella Vieira ; da Cruz, Marcelo Cavalcanti ; Faria, Thaissa Maria Veiga ; Martins, Gisele Eiras ; Mancano, Bruna Minniti ; Lopes, Luiz Fernando ; Reis, Rui Manuel ; Moreno, Daniel Antunes ; Pinto, Mariana Tomazini

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 16, p. 11-pg., 2025-06-20.

Resumo

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. (AU)

• Processo FAPESP: 19/07502-8 - Investigação dos fatores indutores da transição epitélio-mesenquimal (EMT) em tumores de células germinativas
• Beneficiário: Mariana Tomazini Pinto
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 23/07073-5 - Transição epitélio-mesenquimal: implicações em pacientes pediátricos com tumores de células germinativas
• Beneficiário: Lenilson Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado