Human Group IIA Secreted Phospholipase A₂ and the Prostate Cancer Tumor Microenvironment: Potential Mechanisms

Human secreted phospholipase A₂ group IIA (hGIIA) is a Ca²⁺-dependent extracellular enzyme that supports host defense and amplifies inflammation through lipid mediator generation and receptor-linked signaling. In prostate cancer (PCa), hGIIA is commonly elevated compared with benign tissue and can persist after androgen deprivation, implicating it in tumor progression. PCa is typically an immunologically "cold" disease sustained by an immunosuppressive tumor microenvironment enriched in regulatory T cells ( T_reg), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and pro-tumor stromal cells, alongside hypoxia and metabolic rewiring. Because hGIIA is released by innate immune cells and is inducible in macrophages, it is well positioned to strengthen inflammatory lipid networks and promote immune dysfunction within the prostate tumor microenvironment. Here, we review the PCa microenvironment and evaluate evidence linking hGIIA to tumor-stroma crosstalk, angiogenic programming, and therapy resistance, highlighting major knowledge gaps in prostate-focused immune studies.