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Using immunohistochemistry, multiparametric flow cytometry, and transcriptomics in 59 ITACs, the study finds high CD8+ TIL density associates with improved survival and identifies immune checkpoints, macrophage TIM-3 expression, CD155 without PDL1, and hot versus cold tumor immune phenotypes with different prognostic and response implications.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/oncoimmunology-research-article-unveiling-the-immune-microenvironment-in-sinonasal-intestinal-type-adenocarcinoma-new-arguments-for-immunotherapy/356171/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/oncoimmunology-research-article-unveiling-the-immune-microenvironment-in-sinonasal-intestinal-type-adenocarcinoma-new-arguments-for-immunotherapy/356171.png","ImageObject",300,407,{"name":42,"@type":43},"acoobca","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What makes sinonasal intestinal-type adenocarcinoma (ITAC) clinically challenging to treat?","Question",{"text":63,"@type":64},"ITAC is rare and often associated with occupational wood-dust exposure. Standard treatments provide limited benefit for advanced or recurrent disease, and dedicated clinical studies of immune checkpoint inhibitors in ITAC are lacking.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the study assess the ITAC immune microenvironment?",{"text":68,"@type":64},"The immune microenvironment was evaluated in ITACs (n=59) using immunohistochemistry, multiparametric flow cytometry, and transcriptomic profiling.",{"name":70,"@type":61,"acceptedAnswer":71},"Which immune features were linked to better prognosis or therapy response in ITAC?",{"text":72,"@type":64},"Higher CD8+ T-cell densities correlated with improved disease-free and overall survival, and transcriptomic analysis identified a “hot tumor” cluster with adaptive immune activation, better prognosis, and higher immunotherapy response score.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},356171,1790216950,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},3985747870733,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","ONCOIMMUNOLOGY  \n2026, VOL. 15, NO. 1, 2725500  \n[https://doi.org/10.1080/2162402X.2026.2725500](https://doi.org/10.1080/2162402X.2026.2725500)  \nRESEARCH ARTICLE     \nUnveiling the immune microenvironment in sinonasal intestinal type adenocarcinoma: new arguments for immunotherapy  \nCharles Lépinea, b, Cécile Deleineb, Richard Dangerc, Laura Do Souto Ferreirad, Elisabeth Nguyenc, Marie-Anne Vibete, Olivier Malardf, Nadine Gervoisb, Karine Renaudina,c, 1 and Anne Jarryb, 1   \naNantes Université, CHU de Nantes, Pathology Department, Nantes, France; bNantes Université, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR1302/EMR6001, Nantes, France; cNantes Université, CHU de Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR1064, Nantes, France; dNantes Université, CHU de Nantes, Medical Genetic Department, Nantes, France; eNantes Université, CHU de Nantes, Research and Innovation Department, Nantes, France; fNantes Université, CHU de Nantes, Department of Otorhinolaryngology and Head and Neck Surgery, Nantes, France  \nABSTRACT  \nSinonasal intestinal-type adenocarcinoma (ITAC) is a rare malignancy strongly associated with occupational exposure to wood dust that shares morphological and molecular similarities with colorectal adenocarcinoma. Standard treatments offer limited benefit for advanced or recurrent disease. It is therefore necessary to develop other strategies, such as immunotherapies, which require a better understanding of the tumor immune microenvironment, are needed. In this study, we investigated the immune microenvironment of ITACs (n=59), focusing on tumor-infiltrating T lymphocytes (TILs) and macrophages, in situ using immunohistochemistry, ex vivo by multiparametric flow cytometry, as well as by transcriptomic profiling. High CD8⁺ T-cell densities were associated with significantly improved disease-free and overall survival and emerged as an independent prognostic factor. These TILs express immune checkpoints (IC), the most highly expressed being PD1, TIGIT, and TIM-3 . Furthermore, TIM-3 was not only expressed by TILs but also by immunoregulatory macrophages, and may represent an important immune escape mechanism in ITACs, since TIM-3 blockade inpatient-derived explants led to increased tumor cell apoptosis. Tumor cells strongly expressed CD155 (TIGIT ligand) but not PDL1 (PD1 ligand); however expressed by myeloid cells. Finally, transcriptomic analyses identified one cluster displaying features of “hot tumors” characterized by adaptive immune activation, a better prognosis, and a higher immunotherapy response score, and another cluster with features of “cold tumors”. These first exploratory and descriptive findings in ITACs provide a rationale for further investigations using ex vivo and in vivo models to evaluate the therapeutic potential of immunotherapies in these rare cancers.  \nARTICLE HISTORY  \nReceived 7 April 2026 Revised 15 June 2026 Accepted 16 July 2026  \nKEYWORDS  \nImmunotherapy; sinonasal intestinal type adenocarcinoma (ITAC); tumor immune microenvironment; immune checkpoints; transcriptomics; patient-derived explants  \nIntroduction  \nSinonasal intestinal-type adenocarcinoma (ITAC) is a rare entity limited to the nasal cavity and paranasal sinuses. 1 It is considered an occupational disease, typically associated with exposure to wood dust.2-4 The disease may occur decades after exposure.5 ITACs display morphological features closely resembling those of adenocarcinomas of the gastrointestinal tract. Histologically, ITACs can be subdivided into several morphologic subtypes: papillary or well-differentiated, colonic or moderately differentiated, solid or poorly differentiated, and mucinous with or without signet ring cells. Mixed patterns, particularly those combining mucinous and other subtypes, can be observed. Mucinous ITACs with signet ring cells are associated with the poorest prognosis.6,7  \nIn addition to their morphological similarities","cbCaiawrFkusPV2b","https://ap.wps.com/l/cbCaiawrFkusPV2b","pdf",3899027,15,"English","# Abstract\n# Introduction\n## Occupational association and rarity of ITAC\n## Morphologic and molecular parallels with colorectal adenocarcinoma\n## Current treatment limitations and rationale for immunotherapy\n# Materials and Methods\n# Results\n# Discussion","[{\"question\":\"What makes sinonasal intestinal-type adenocarcinoma (ITAC) clinically challenging to treat?\",\"answer\":\"ITAC is rare and often associated with occupational wood-dust exposure. Standard treatments provide limited benefit for advanced or recurrent disease, and dedicated clinical studies of immune checkpoint inhibitors in ITAC are lacking.\"},{\"question\":\"How did the study assess the ITAC immune microenvironment?\",\"answer\":\"The immune microenvironment was evaluated in ITACs (n=59) using immunohistochemistry, multiparametric flow cytometry, and transcriptomic profiling.\"},{\"question\":\"Which immune features were linked to better prognosis or therapy response in ITAC?\",\"answer\":\"Higher CD8+ T-cell densities correlated with improved disease-free and overall survival, and transcriptomic analysis identified a “hot tumor” cluster with adaptive immune activation, better prognosis, and higher immunotherapy response score.\"}]","ONCOIMMUNOLOGY - Research Article - Unveiling the immune microenvironment in sinonasal intestinal type adenocarcinoma: new arguments for immunotherapy | PDF",1790123852,38]