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This mini review explains myeloid-centric immune failure through macrophage, dendritic-cell, and neutrophil programs revealed by single-cell RNA/ATAC and spatial transcriptomics. It highlights translational opportunities and limits, including HPV-status heterogeneity, limited assay standardization, and scarce predictive metrics, and proposes integrating myeloid biomarkers with PD-1-, EGFR-, and myeloid-checkpoint strategies.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/myeloid-driven-immunosuppression-in-head-and-neck-cancer-single-cell-atacrna-and-spatial-transcriptomic-perspectives/410167/",{"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/myeloid-driven-immunosuppression-in-head-and-neck-cancer-single-cell-atacrna-and-spatial-transcriptomic-perspectives/410167.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why do immune-checkpoint inhibitors benefit only a subset of HNSCC patients?","Question",{"text":113,"@type":114},"Durable benefit is limited because immune failure is driven by myeloid-centric mechanisms within the tumor microenvironment, including barriers from specific macrophage programs and impaired antigen presentation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which myeloid cell programs are emphasized in this review?",{"text":118,"@type":114},"The review focuses on tumor-associated macrophages, dendritic-cell programs, and neutrophil states, describing how they contribute to immunosuppression and adverse prognosis.",{"name":120,"@type":111,"acceptedAnswer":121},"How do single-cell ATAC/RNA and spatial transcriptomics support myeloid-informed precision immuno-oncology?",{"text":122,"@type":114},"They resolve macrophage, dendritic-cell, and neutrophil programs at high resolution and map spatial tumor-stroma interfaces, enabling evaluation of translational opportunities and myeloid biomarkers for clinical strategies.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},410167,1790640770,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":44,"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,"preview_page_count":4},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","TYPE Mini Review  \nPUBLISHED 18 December 2025 DOI 10.3389/fonc.2025.1693152  \nOPEN ACCESS  \nEDITED BY  \nJohn Maher,  \nKing’s College London, United Kingdom  \nREVIEWED BY  \nShaoqiu Chen,  \nUniversity of Hawaii at M¯anoa, United States Jinyan Yang,  \nSouthwest Medical University, China  \n*CORRESPONDENCE  \nZimeng Cao  \n [m18580568188@163.com](m18580568188@163.com)[ ](m18580568188@163.com)Bing Li  \n [dclibing@sina.com](dclibing@sina.com)  \n†These authors have contributed equally to this work  \nRECEIVED 26 August 2025  \nREVISED 31 October 2025  \nACCEPTED 13 November 2025  \nPUBLISHED 18 December 2025  \nCORRECTED 06 March 2026  \nCITATION  \nLuo R, Yang J, Cao Z and Li B (2025)  \nMyeloid-driven immunosuppression in head and neck cancer: single-cell ATAC/RNA and spatial transcriptomic perspectives.  \nFront. Oncol. 15:1693152 .  \ndoi: 10.3389/fonc.2025.1693152  \nCOPYRIGHT  \n© 2025 Luo, Yang, Cao and Li. This is an openaccess 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.  \nMyeloid-driven immunosuppression in head and neck cancer: single-cell ATAC/RNA and spatial transcriptomic perspectives  \nRui Luo 1,2†, Jianzheng Yang 3†, Zimeng Cao 4* and Bing Li 1*  \n1 Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, 2 Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing, China, 3 Department of Ultrasound, Chongqing Nan’an District People’s Hospital, Chongqing, China, 4 Department of Laboratory Medicine, Chonggang General Hospital, Chongqing, China  \nHead and neck squamous cell carcinoma (HNSCC) remains a prevalent epithelial malignancy. Immune-checkpoint inhibitors have reshaped first-line therapy for recurrent/metastatic disease; yet durable benefit is confined to a subset, reflecting myeloid-centric mechanisms—SPP1+ TAM barriers, cDC1/IL-12 insufficiency, and CXCL8–CXCR1/2–driven neutrophil trafficking—distinct from, and complementary to, classical lymphoid exhaustion. In this review we summarize advances from single-cell RNA and ATAC profiling and spatial transcriptomics that resolve macrophage, dendritic-cell and neutrophil programs, and appraise translational opportunities spanning myeloid reprogramming, innate–adaptive combinations and spatial biomarkers. We also discuss enduring challenges—including HPV-status heterogeneity, limited assay standardization and a scarcity of predictive metrics—that temper implementation. By integrating myeloid-informed readouts (e. g., SPP1–TAM burden, cDC1 competency, serum IL-8) with PD-1–based regimens, EGFRdirected antibodies and myeloid checkpoints (CD47–SIRPa, PI3Kg, CXCR1/2), emerging strategies aim to restore antigen presentation, improve lymphocyte trafficking and remodel tumor–stroma interfaces. Our synthesis provides an appraisal of the evolving landscape of myeloid-informed precision immunooncology in HNSCC and outlines pragmatic standards and avenues for clinical translation. We hope these insights will assist researchers and clinicians as they endeavor to implement more effective, individualized regimens.  \nKEYWORDS  \nhead and neck squamous cell carcinoma, myeloid reprogramming, single-cell RNA/ ATAC, spatial transcriptomics, checkpoint blockade, PD-1/PD-L1  \nFrontiers in Oncology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nHead and neck squamous cell carcinoma (HNSCC) remains a common epithelial malignancy with heterogeneous etiologies and outcomes, including tobacco- and alcohol-associated disease and virally driven subsets (1–3), and immune checkpoint inhibitors have become part of first-lin","cbCaikK80OkvU97N","https://ap.wps.com/l/cbCaikK80OkvU97N","pdf",991072,"English","# Introduction\n## Myeloid-driven immunosuppression in HNSCC\n## Single-cell RNA sequencing contributions\n## Goals and clinical translation","[{\"question\":\"Why do immune-checkpoint inhibitors benefit only a subset of HNSCC patients?\",\"answer\":\"Durable benefit is limited because immune failure is driven by myeloid-centric mechanisms within the tumor microenvironment, including barriers from specific macrophage programs and impaired antigen presentation.\"},{\"question\":\"Which myeloid cell programs are emphasized in this review?\",\"answer\":\"The review focuses on tumor-associated macrophages, dendritic-cell programs, and neutrophil states, describing how they contribute to immunosuppression and adverse prognosis.\"},{\"question\":\"How do single-cell ATAC/RNA and spatial transcriptomics support myeloid-informed precision immuno-oncology?\",\"answer\":\"They resolve macrophage, dendritic-cell, and neutrophil programs at high resolution and map spatial tumor-stroma interfaces, enabling evaluation of translational opportunities and myeloid biomarkers for clinical strategies.\"}]","Myeloid-driven immunosuppression in head and neck cancer - single-cell ATAC/RNA and spatial transcriptomic perspectives | PDF",1790584481,23]