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Pyroptosis-Related Pathways and Their Impact on Immune Microenvironment Remodeling in Pediatric Ovarian and Adnexal
Chao Sun1, Lei Zhang1, Xiang Li1
1Department of Pediatric Surgery, Qilu Hospital of Shandong University, Qingdao, Shandong Province, China.
Abstract:
Pyroptosis is a gasdermin-mediated form of inflammatory cell death that may alter tumour-immune interactions. Its canonical, non-canonical and granzyme-associated pathways, together with NINJ1-dependent terminal membrane rupture, are reviewed here. Whether these mechanisms promote antitumour immunity or sustained inflammation depends on biological context. Pediatric ovarian and adnexal neoplasms include germ-cell tumours (GCTs), sex cord-stromal tumours (SCSTs), and less-common epithelial or other lesions. Histology, age, pubertal status, hormonal secretion, stage, and treatment exposure vary substantially across patients. Direct studies of pyroptosis and immune remodelling in these paediatric histologies remain scarce; evidence from adult epithelial ovarian cancer, non-ovarian tumours, cell lines, and mice cannot be treated as proof of a paediatric mechanism. This review retains a histology-specific framework to examine molecular pathways, the paediatric ovarian tumour immune microenvironment (TIME), candidate therapeutic approaches, and biomarkers. Established molecular or clinical observations are separated from cross-tumour extrapolations and untested hypotheses. Particular attention is paid to developmental immunity, endocrine context, on-target and off-target inflammation, and evidence required before clinical translation.
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