{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:33:10Z","timestamp":1790530390865,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"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:p>Prostate cancer (PCa) is still as a major cause of morbidity and mortality in men at the global level, highlighting the necessity for improved diagnostic and therapeutic strategies beyond current PSA screening limitations. This mini-review focuses on the complex and often opposing roles of two key cytokines, IL-33 and IL-38, within the tumour microenvironment and their implications for host immunosurveillance in PCa. Intra-tumoral IL-33 expression is significantly reduced in PCa tissues and correlates with aggressive disease features such as higher Gleason scores and lymphatic metastasis, suggesting an inherent anti-tumour function. Such a protective role may be mediated <jats:italic>via<\/jats:italic> the ST2\/NF-\u03baB signalling pathway and the recruitment of lymphocytes into the tumour microenvironment. However, a paradoxical increase in circulating IL-33 levels in PCa patients hints at complex systemic compensatory mechanisms or differential compartmental regulation. In contrast, intra-tumoral IL-38 exhibits markedly elevated expression in PCa compared to benign prostatic hyperplasia and non-cancerous tissues. This increased IL-38 correlates with tumour severity, advanced TNM stages, and poorer overall survival, indicating a pro-tumoral role. Mechanistically, IL-38 appears to inhibit CD8<jats:sup>+<\/jats:sup> cytotoxic T cell infiltration and potentially promotes immunosuppression through the upregulation of regulatory T cells (Tregs), thereby facilitating tumour progression. The contrasting expression patterns and clinicopathological associations of IL-33 and IL-38 highlight their potential as novel biomarkers for PCa diagnosis and prognosis. Further comprehensive investigation, including multi-centre studies across diverse populations, functional <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> analyses, and exploration of their therapeutic targetability, is crucial to translate these findings into effective precision medicine strategies for PCa patients.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1623038","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T05:45:39Z","timestamp":1750225539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The differential role of IL-33 and IL-38 in prostate cancer, contradictory 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