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Robust, persistent inflammatory programs drive tumor initiation and progression while simultaneously creating therapeutic vulnerabilities and barriers by reshaping immune-cell states and the tumor immune microenvironment. This review explains how chronic inflammatory cues rewire immune signaling and tissue architecture, catalogues inflammation-linked pathways, biomarkers, and micro-niche interactions, and outlines ecology-aware precision combinations to improve outcomes.",{"@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/inflammation-as-a-master-regulator-of-immunotherapy-response-in-head-and-neck-squamous-cell-carcinoma-from-malignant-transformation-to-ecology-aware-precision-combinations/353312/",{"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/inflammation-as-a-master-regulator-of-immunotherapy-response-in-head-and-neck-squamous-cell-carcinoma-from-malignant-transformation-to-ecology-aware-precision-combinations/353312.png","ImageObject",300,407,{"name":92,"@type":93},"kopisore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why does inflammation strongly influence immunotherapy response in HNSCC?","Question",{"text":112,"@type":113},"Inflammation is robust and persistent in HNSCC, driving tumor initiation and progression while also altering immune-cell behavior and the immune microenvironment. This can create both therapeutic vulnerabilities and resistance barriers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which immune cells and dendritic cell subsets are highlighted as plastic under inflammatory pressure?",{"text":117,"@type":113},"Macrophages, regulatory T cells, exhausted CD8+ T cells, and specialized dendritic cell subsets can switch roles between tumor-clearing functions and promoters of tumor growth, stemness, and invasion.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the review connect specific signaling pathways and biomarkers to immune-state changes?",{"text":121,"@type":113},"It links pathways such as NF-kB/STAT3, IL-6/TNFa, TGF-b, HA-CD44, and PI3K-4EBP1-SOX2 to trade-offs governing proliferation, invasion, and cancer stem cell dynamics. Corresponding biomarkers (e.g., PD-L1 and myeloid-related ratios) become more informative when resolved at single-cell and spatial scales for patient stratification.","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},353312,1790197025,{"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":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","TYPE Review  \nPUBLISHED 17 July 2026  \nDOI 10.3389/fimmu.2026.1798938  \nOPEN ACCESS  \nEDITED BY  \nShisong Jiang,  \nUniversity of Oxford, United Kingdom  \nREVIEWED BY  \nChen Feng,  \nShandong University, China Roberto Rangel,  \nUniversity of Texas MD Anderson Cancer Center, United States  \n*CORRESPONDENCE  \nJia Gu  \n [gujia19840128@aliyun.com](gujia19840128@aliyun.com)[ ](gujia19840128@aliyun.com)Zhaozhe Liu  \n [lzz_summer@126.com](lzz_summer@126.com)[ ](lzz_summer@126.com)Zhenguang Du  \n [bone_tumor@sina.com](bone_tumor@sina.com)[ ](bone_tumor@sina.com)†These authors have contributed equally to this work and share first authorship  \nRECEIVED 29 January 2026  \nREVISED 05 June 2026  \nACCEPTED 26 June 2026  \nPUBLISHED 17 July 2026  \nCITATION  \nHan Y, Wu P, Song H, Yu R, Liu R, Du Z, Liu Z and Gu J (2026) Inflammation as a master regulator of immunotherapy response in head and neck squamous cell carcinoma: from malignant transformation to ecology-aware precision combinations.  \nFront. Immunol. 17:1798938 .  \ndoi: 10.3389/fimmu.2026.1798938  \nCOPYRIGHT  \n© 2026 Han, Wu, Song, Yu, Liu, Du, Liu and Gu. This is an open-access article distributed under the terms of the  \nCreative 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.  \nInflammation as a master regulator of immunotherapy response in head and necksquamous cell carcinoma:  \nfrom malignant transformation to ecology-aware  \nprecision combinations  \nYingchen Han 1†, Peihong Wu 1†, Haoran Song 1†, Ruoxi Yu 2, Ruotong Liu 3, Zhenguang Du 4*, Zhaozhe Liu 5* and Jia Gu 2*  \n1 Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China, 2 Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China, 3Shenyang Medical College, Shenyang, Liaoning, China,  \n4 Department of Interventional Medicine, Liaoning Provincial People’s Hospital, Shenyang, Liaoning, China, 5 Department of Oncology, General Hospital of the Northern Theater Command, Shenyang, Liaoning, China  \nIn the era of immunotherapy, head and neck squamous cell carcinoma (HNSCC) has demonstrated clear benefits from immune-based treatments and is widely regarded as a tumor type with high immunotherapeutic potential. These tumors are characterized by robust and persistent inflammatory responses that actively drive tumor initiation and progression while concurrently shaping their sensitivity or resistance to therapy. Inflammation simultaneously creates therapeutic vulnerabilities and barriers by altering tumor behavior and reprogramming the immune microenvironment. This review examined HNSCC through a tripartite prism of inflammation, immunity, and tumor biology to demonstrate how chronic inflammatory cues rewire immune cells, reshape signaling circuits, and remodel tissue architecture, ultimately altering responses to immunotherapy. We first examined how immune cell reprogramming occurs under inflammatory pressure. Macrophages, regulatory T cells, exhausted CD8+ T cells, and specialized dendritic cell subsets can switch roles—from tumor-clearing sentinels to promoters of tumor growth, stemness, and invasion. This plasticity—sometimes transient, sometimes entrenched—determines whether the immune ecosystem favors elimination or tolerance, and consequently whether immune checkpoint blockade succeeds or fails. Next, we catalogued the inflammation-linked pathways and readouts that capture these state changes. Signaling hubs such as NF-kB/STAT3, IL-6/TNFa, TGF-b, HA-CD44, and PI3K-4EBP1-SOX2 orchestrate the trade-offs between proliferation and invasion and govern cancer stem cell dynamics. Corresponding biomarkers—PD-L1, C","cbCaikVr5b2m8ONj","https://ap.wps.com/l/cbCaikVr5b2m8ONj","pdf",15727139,"English","# Introduction\n## Inflammation, immunity, and tumor biology framework\n## Immune cell reprogramming under inflammatory pressure\n## Inflammation-linked pathways and biomarkers\n## Pathological interplay across tumor, stromal, and immune compartments\n## Translational directions for precision immunotherapy","[{\"question\":\"Why does inflammation strongly influence immunotherapy response in HNSCC?\",\"answer\":\"Inflammation is robust and persistent in HNSCC, driving tumor initiation and progression while also altering immune-cell behavior and the immune microenvironment. This can create both therapeutic vulnerabilities and resistance barriers.\"},{\"question\":\"Which immune cells and dendritic cell subsets are highlighted as plastic under inflammatory pressure?\",\"answer\":\"Macrophages, regulatory T cells, exhausted CD8+ T cells, and specialized dendritic cell subsets can switch roles between tumor-clearing functions and promoters of tumor growth, stemness, and invasion.\"},{\"question\":\"How does the review connect specific signaling pathways and biomarkers to immune-state changes?\",\"answer\":\"It links pathways such as NF-kB/STAT3, IL-6/TNFa, TGF-b, HA-CD44, and PI3K-4EBP1-SOX2 to trade-offs governing proliferation, invasion, and cancer stem cell dynamics. Corresponding biomarkers (e.g., PD-L1 and myeloid-related ratios) become more informative when resolved at single-cell and spatial scales for patient stratification.\"}]","Inflammation as a master regulator of immunotherapy response in head and neck squamous cell carcinoma - from malignant transformation to ecology-aware precision combinations | PDF",1790104656,48]