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In prostate cancer (PCa), hGIIA is often elevated relative to benign tissue and can persist after androgen deprivation, suggesting a role in tumor progression. PCa is commonly immunologically “cold,” driven by an immunosuppressive microenvironment enriched in Treg, MDSCs, TAMs, and pro-tumor stromal cells, along with hypoxia and metabolic rewiring. Because hGIIA is released by innate immune cells and inducible in macrophages, it may enhance inflammatory lipid networks and contribute to immune dysfunction. This review evaluates evidence linking hGIIA to tumor–stroma crosstalk, angiogenic programs, and therapy resistance, and identifies key gaps in prostate-focused immune studies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/human-group-iia-secreted-phospholipase-a-2-and-the-prostate-cancer-tumor-microenvironment-potential-mechanisms/354662/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/human-group-iia-secreted-phospholipase-a-2-and-the-prostate-cancer-tumor-microenvironment-potential-mechanisms/354662.png","ImageObject",300,407,{"name":92,"@type":93},"LangkahRina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-25","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does hGIIA play in normal host defense and inflammation?","Question",{"text":112,"@type":113},"hGIIA is a Ca2+-dependent extracellular enzyme that supports host defense and amplifies inflammation by generating lipid mediators and activating receptor-linked signaling pathways.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is hGIIA considered important in prostate cancer progression?",{"text":117,"@type":113},"hGIIA is commonly elevated in prostate cancer tissues versus normal tissue and can persist after androgen deprivation, which implicates it in tumor persistence and aggressiveness.",{"name":119,"@type":110,"acceptedAnswer":120},"How might the prostate tumor microenvironment contribute to immune dysfunction in PCa?",{"text":121,"@type":113},"PCa is described as immunologically “cold,” sustained by an immunosuppressive tumor microenvironment enriched in regulatory T cells, MDSCs, TAMs, and pro-tumor stromal cells, together with hypoxia and metabolic rewiring.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},354662,1790181641,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nHuman Group IIA Secreted Phospholipase A 2 and the Prostate Cancer Tumor Microenvironment: Potential Mechanisms  \nMonavvar Andarva 1,2, Maria George Elias 1,2, Mila Sajinovic 1,2,3, Tara Laurine Roberts 1,2, Paul de Souza 1,3 and Kieran F. Scott 1, *  \nAcademic Editor: Marta Menegazzi  \nReceived: 1 June 2026  \nRevised: 12 August 2026  \nAccepted: 12 August 2026  \nPublished: 14 August 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia; [22059348@student.westernsydney.edu.au](22059348@student.westernsydney.edu.au) (M.A.); [m.elias3@westernsydney.edu.au](m.elias3@westernsydney.edu.au) (M.G.E.); [m.sajinovic@westernsydney.edu.au](m.sajinovic@westernsydney.edu.au) (M.S.); [tara.roberts@westernsydney.edu.au](tara.roberts@westernsydney.edu.au) (T.L.R.); [p.desouza@westernsydney.edu.au](p.desouza@westernsydney.edu.au) (P.d.S.)  \n2 Ingham Institute of Applied Medical Research, Liverpool, NSW 2170, Australia  \n3 Nepean Hospital Clinical School, University of Sydney, Kingswood, NSW 2747, Australia  \n* Correspondence: [kieran.scott@westernsydney.edu.au](kieran.scott@westernsydney.edu.au); Tel.: +61-(0)4-1914-3647  \nAbstract  \nHuman secreted phospholipase A 2 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 ( Treg ), 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.  \nKeywords: prostate cancer; tumor microenvironment; secreted phospholipase A 2 group IIA; PLA2G2A; immune modulation  \n1. Introduction  \nThe phospholipase A 2 (PLA 2) superfamily encompasses six structurally distinct enzyme groups that cleave the sn-2 ester bond in phospholipids, producing free fatty acids and lysophospholipids vital for physiological functions. The first group identified in humans was secreted enzymes (sPLA 2s) that exhibit tissue-specific expression. For example, group IB sPLA 2 is normally expressed in the pancreas, while group IIF sPLA 2 is expressed primarily in skin cells [1,2] . The best studied human sPLA2 (hGIIA, group IIA sPLA 2, sPLA2-IIA, PLA2G2A) is involved in host defense against infection in healthy subjects, being expressed in and released from secretory glands such as salivary glands, Paneth cells, the prostate gland, lacrimal glands and the lactating breast. The enzyme is also stored in vesicles of innate immune cells such as mast cells, platelets and neutrophils. Its expression is inducible in other innate immune cells such as macrophages, by pro-inflammatory cytokines such as TNF and IL-1β or Toll-like receptor agonists such as LPS. Consequently, hGIIA is well positioned to be a key molecular factor in regulating innate immunity [3] .  \nImportantly, hGIIA dysregulation is linked to immune-mediated pathologies including cancer, atherosclerosis, neuroinflammation, COVID-19, sepsis, inflammatory bowel disease, and rheumatoid arthritis [4] .","cbCaivJGbDn1yds6","https://ap.wps.com/l/cbCaivJGbDn1yds6","pdf",1096214,33,"English","# Abstract\n## Introduction\n## hGIIA in cancer and prostate tumor microenvironment","[{\"question\":\"What role does hGIIA play in normal host defense and inflammation?\",\"answer\":\"hGIIA is a Ca2+-dependent extracellular enzyme that supports host defense and amplifies inflammation by generating lipid mediators and activating receptor-linked signaling pathways.\"},{\"question\":\"Why is hGIIA considered important in prostate cancer progression?\",\"answer\":\"hGIIA is commonly elevated in prostate cancer tissues versus normal tissue and can persist after androgen deprivation, which implicates it in tumor persistence and aggressiveness.\"},{\"question\":\"How might the prostate tumor microenvironment contribute to immune dysfunction in PCa?\",\"answer\":\"PCa is described as immunologically “cold,” sustained by an immunosuppressive tumor microenvironment enriched in regulatory T cells, MDSCs, TAMs, and pro-tumor stromal cells, together with hypoxia and metabolic rewiring.\"}]","Human Group IIA Secreted Phospholipase A 2 and the Prostate Cancer Tumor Microenvironment: Potential Mechanisms | PDF",1790112819,83]