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This review synthesizes single-cell and spatial omics evidence that reframes prostate cancer as a dynamic metabolic-immune ecosystem. It details how malignant epithelial states, stromal niches, myeloid programs, T-cell exclusion, vascular remodeling, and selection pressures interact to drive progression and therapy resistance, and highlights gaps in treatment-specific evidence and the need for mechanism-matched combinations.",{"@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/single-cell-and-spatial-omics-of-metabolic-immune-ecosystems-in-prostate-cancer-from-androgen-signaling-to-therapy-resistance/352082/",{"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/single-cell-and-spatial-omics-of-metabolic-immune-ecosystems-in-prostate-cancer-from-androgen-signaling-to-therapy-resistance/352082.png","ImageObject",300,407,{"name":92,"@type":93},"RuangKosong","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","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},"Why can’t androgen receptor signaling alone explain prostate cancer behavior?","Question",{"text":112,"@type":113},"Many tumors show castration-resistant-like or lineage- and chromatin-driven programs before or during treatment, and advanced disease often involves immune suppression, stromal remodeling, and metabolic reprogramming that jointly influence response.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What limitations does bulk genomics have for understanding treatment response?",{"text":117,"@type":113},"Bulk tissue averages malignant clones with multiple cell types, so it often cannot assign pathways to specific cell states, determine pre-treatment low-abundance states, or reveal dependence on local niche features such as extracellular matrix, nutrients, and oxygen gradients.",{"name":119,"@type":110,"acceptedAnswer":120},"How do single-cell and spatial omics advance the ecosystem model of prostate cancer?",{"text":121,"@type":113},"They enable direct measurement of malignant and microenvironment states, mapping epithelial hierarchies, niche programs, immune neighborhood features, and spatially resolved metabolic dependencies that shape progression and resistance.","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},352082,1790192904,{"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},962090883219,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","TYPE Review  \nPUBLISHED 06 August 2026  \nDOI 10.3389/fimmu.2026.1899588  \nOPEN ACCESS  \nEDITED BY  \nYunfei Liu,  \nCentral South University, China  \nREVIEWED BY  \nDekai Zhang,  \nTexas A&M University, United States Ninghong Song,  \nNanjing Medical University, China Danial Hashemi Karoii, University of Tehran, Iran  \n*CORRESPONDENCE  \nYifan Li  \n [092107@yzu.edu.cn](092107@yzu.edu.cn)[ ](092107@yzu.edu.cn)Xiaoxiang Wang  \n[18936489811@163.com](18936489811@163.com)[ ](18936489811@163.com)RECEIVED 03 June 2026 REVISED 17 July 2026 ACCEPTED 28 July 2026 PUBLISHED 06 August 2026  \nCITATION  \nWang R, Li Y and Wang X (2026)  \nSingle-cell and spatial omics of metabolic-immune ecosystems in prostate cancer: from androgen signaling to therapy resistance.  \nFront. Immunol. 17:1899588 .  \ndoi: 10.3389/fimmu.2026.1899588  \nCOPYRIGHT  \n© 2026 Wang, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nSingle-cell and spatial omics of metabolic-immune ecosystems in prostate cancer: from androgen signaling to therapy resistance  \nRuiang Wang 1, Yifan Li 2* and Xiaoxiang Wang 2*  \n1The First Clinical Medical College, Faculty of Medicine, Yangzhou University, Yangzhou, China, 2 Department of Urology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China  \nProstate cancer is a hormone-driven malignancy, but its clinical behavior cannot be explained by androgen receptor (AR) signaling alone. Single-cell and spatial omics are redefining prostate cancer as an evolving metabolic-immune ecosystem in which malignant epithelial states, stromal niches, myeloid programs, T-cell exclusion, vascular remodeling, and treatment-imposed selection pressures jointly shape progression and resistance. These technologies have resolved the normal prostate epithelial hierarchy, pre-existing castration-resistant-like cells, basal-like, club-like, and hillock-like programs, neuroendocrine transformation states, immunosuppressive macrophage populations, fibroblast states, and spatial neighborhoods that aredifficult to detect by bulk sequencing. Treatment-associated changes have been characterized most directly in androgen-axis and immune contexts, whereas evidence related to taxanes, DNA damage response (DDR)-targeted therapy, and radioligand therapy remains emerging or hypothesis-generating. This review synthesizes single-cell and spatial omics evidence for metabolic-immune ecosystems in prostate cancer, emphasizing the transition from androgen dependence to castration resistance, lineage plasticity, metastatic niche adaptation, and therapy resistance. We argue that the next translational step is not simply to catalog additional cell types, but to connect longitudinal cell-state maps, spatially resolved metabolic dependencies, immune-neighborhood biomarkers, and mechanismmatched combination therapies.  \nKEYWORDS  \nandrogen receptor, castration resistance, metabolism, neuroendocrine prostate cancer, prostate cancer, single-cell RNA sequencing, spatial transcriptomics, therapy resistance  \n1 Introduction  \nProstate cancer has traditionally been understood through an endocrine lens: malignant growth depends on androgen receptor (AR) activity, androgen deprivation therapy (ADT) can induce tumor regression, and most lethal tumors ultimately reactivate AR signaling or escape AR dependence. This framework remains clinically useful, as next-generation AR signaling inhibitors (ARSIs), taxanes, poly(ADP-ribose) polymerase (PARP) inhibitors for selected  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nDNA repair-defective tumors, and p","cbCaidGksqQyD0S3","https://ap.wps.com/l/cbCaidGksqQyD0S3","pdf",3611074,18,"English","# Introduction\n## Prostate cancer beyond androgen-centric models\n## Limits of bulk genomics and advantages of omics\n## Ecosystem framework for metabolic-immune interactions","[{\"question\":\"Why can’t androgen receptor signaling alone explain prostate cancer behavior?\",\"answer\":\"Many tumors show castration-resistant-like or lineage- and chromatin-driven programs before or during treatment, and advanced disease often involves immune suppression, stromal remodeling, and metabolic reprogramming that jointly influence response.\"},{\"question\":\"What limitations does bulk genomics have for understanding treatment response?\",\"answer\":\"Bulk tissue averages malignant clones with multiple cell types, so it often cannot assign pathways to specific cell states, determine pre-treatment low-abundance states, or reveal dependence on local niche features such as extracellular matrix, nutrients, and oxygen gradients.\"},{\"question\":\"How do single-cell and spatial omics advance the ecosystem model of prostate cancer?\",\"answer\":\"They enable direct measurement of malignant and microenvironment states, mapping epithelial hierarchies, niche programs, immune neighborhood features, and spatially resolved metabolic dependencies that shape progression and resistance.\"}]","Single-cell and spatial omics of metabolic-immune ecosystems in prostate cancer - from androgen signaling to therapy resistance | PDF",1790097598,45]