[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332633-105":59,"doc-detail-332633-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","the-prognostic-and-therapeutic-value-of-the-tumor-microenvironment-and-immune-checkpoints-in-pancreatic-neuroendocrine-neoplasms","The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms","","Pancreatic neuroendocrine neoplasms (Pan-NEN) show heterogeneous biology and challenging clinical outcomes. The study systematically characterizes the tumor microenvironment (TME) to identify immunological prognostic biomarkers and to assess immunotherapy potential. Tumor and adjacent normal tissues from 56 Pan-NEN patients were analyzed by immunohistochemistry using monoclonal antibodies for immune markers. Low CD3/CD8/CD4/CD68/CD163/Foxp3 and checkpoint marker expression was common, with PD-1/PD-L1 and macrophage-related markers differing by differentiation grade and correlating with stage and survival. Univariate and multivariate Cox analyses supported PD-1 expression as an independent prognostic factor, suggesting PD-1/PD-L1–targeted immunotherapy may benefit Pan-NEN, especially Pan-NEC.",{"@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/the-prognostic-and-therapeutic-value-of-the-tumor-microenvironment-and-immune-checkpoints-in-pancreatic-neuroendocrine-neoplasms/332633/",{"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/the-prognostic-and-therapeutic-value-of-the-tumor-microenvironment-and-immune-checkpoints-in-pancreatic-neuroendocrine-neoplasms/332633.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main objective of the study on Pan-NEN immunology?","Question",{"text":112,"@type":113},"To systematically investigate immunological features of the tumor microenvironment in pancreatic neuroendocrine neoplasms, identify prognostic biomarkers, and evaluate therapeutic potential for immunotherapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were immune markers assessed in Pan-NEN samples?",{"text":117,"@type":113},"Tumor and adjacent normal tissues from 56 patients were analyzed using immunohistochemical staining with a panel of monoclonal antibodies targeting key immune markers.",{"name":119,"@type":110,"acceptedAnswer":120},"Which immune checkpoint–related factor showed independent prognostic value?",{"text":121,"@type":113},"PD-1 expression was identified as an independent prognostic factor in multivariate Cox proportional hazard analyses, and PD-1/PD-L1 targeting is suggested as a promising strategy.","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},332633,1790379329,{"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":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"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,"preview_page_count":4},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nThe prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms  \nZhijiang Chen1,2, Shizhao Lin1,2, Feihong Liang1, Zelin Hou1, Yuanyuan Yang1, Heguang Huang1􀀍 & Yu Pan1􀀍  \nPancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PDL1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in  \nPan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 +cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.  \nKeywords Pancreatic neuroendocrine tumors, Immunoenvironment, Checkpoint  \nPancreatic neuroendocrine neoplasms (Pan-NEN) are a diverse and complex group of neoplasms that originate from both epithelial and neuroendocrine tissues and constitute approximately 5% of all pancreatic neoplasms1. They are pathologically classified into well-differentiated neuroendocrine tumors (Pan-NET) and poorly differentiated neuroendocrine carcinomas (Pan-NEC)2,3, which is a particularly aggressive variant4. Notably, the incidence of these neoplasms has been incrementally increasing, with recent estimates ranging from 0.48 to 1.01 per 100,000 individuals. Furthermore, approximately 20–64% of Pan-NEN patients are diagnosed with distant metastasis at the time of initial presentation5. A combination of surgical resection and targeted therapies has been shown to be effective for early-stage Pan-NEN6; however, the management of metastatic and recurrent  \n1Department of General Surgery, The Cancer Center, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou 350001, People’s Republic of China. 2Zhijiang Chen and Shizhao Lin contributed equally to this work.  \n􀀍 email: [heguanghuang22@163.com](heguanghuang22@163.com); [yupan199002@163.com](yupan199002@163.com)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nPan-NEN remains a significant challenge. Sunitinib7 and Everolimus","cbCaibF9yecsviq2","https://ap.wps.com/l/cbCaibF9yecsviq2","pdf",2286621,"English","# Materials and methods\n## Sample collection","[{\"question\":\"What is the main objective of the study on Pan-NEN immunology?\",\"answer\":\"To systematically investigate immunological features of the tumor microenvironment in pancreatic neuroendocrine neoplasms, identify prognostic biomarkers, and evaluate therapeutic potential for immunotherapy.\"},{\"question\":\"How were immune markers assessed in Pan-NEN samples?\",\"answer\":\"Tumor and adjacent normal tissues from 56 patients were analyzed using immunohistochemical staining with a panel of monoclonal antibodies targeting key immune markers.\"},{\"question\":\"Which immune checkpoint–related factor showed independent prognostic value?\",\"answer\":\"PD-1 expression was identified as an independent prognostic factor in multivariate Cox proportional hazard analyses, and PD-1/PD-L1 targeting is suggested as a promising strategy.\"}]","The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms | PDF",1789998967,25]