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Transcriptomic and single-cell analyses assess pathway enrichment and cell–cell interactions within the mCRC immune microenvironment.",{"@graph":14,"@context":71},[15,34,54],{"@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/research-report/","Research & 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cells?",{"text":70,"@type":62},"Cell–cell communication analysis highlighted Galectin-9–TIM-3 signaling as uniquely present in LAG3+ CD8+ T cells.","https://schema.org",{"og:url":32,"og:type":73,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":75,"canonical":32},"index,follow",{"doc_id":77,"site_id":7},362534,1790174230,{"code":4,"msg":80,"data":81},"success",[82,86,90,94,99,104,109,113,118,121,125],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":83,"show_sort_weight":84,"slug":85},"Story & 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\n[https://doi.org/10.1007/s00262-026-04344-9](https://doi.org/10.1007/s00262-026-04344-9)  \nClinical and immunological implications of lymphocyte‑activation gene 3 expression in metastatic colorectal cancer  \nYi‑Hsuan Huang1 · Shang‑Yin Wu1 · Chung‑Ta Lee2 · Bing‑Syuan Chung1 · Peng‑Chan Lin1 · Ren‑Hao Chan3 · Po‑Chuan Chen3 · Bo‑Wen Lin3 · Meng‑Ru Shen4 · Shang‑Hung Chen1,5 · Yu‑Min Yeh1  \nReceived: 7 November 2025 / Accepted: 16 February 2026 © The Author(s) 2026  \nAbstract  \nBackground Lymphocyte-activation gene 3 (LAG3), an inhibitory immune checkpoint receptor, has emerged as a potential therapeutic target in various cancer, including colorectal cancer (CRC) . However, its prognostic role and immunologic context in metastatic CRC (mCRC) remain unclear. This study investigated the prognostic impact of LAG3 expression and its biological role within the mCRC immune microenvironment.  \nMethods LAG3 expression was evaluated by immunohistochemistry in primary and/or metastatic tumors from a retrospective mCRC cohort. Associations between LAG3 expression, clinicopathological features, and overall survival were analyzed and validated using data from The Cancer Genome Atlas (TCGA) COADREAD cohort. Transcriptomic data from TCGA and single-cell RNA sequencing data from 23 Korean CRC samples were used to explore pathway enrichment and cell–cell interactions.  \nResults A total of 144 mCRC patients were included. Primary tumors showed higher LAG3 expression than metastatic tumors, with right-sided and liver metastases exhibiting the highest level. Both univariate and multivariate analyses revealed that LAG3 expression was an independent prognostic biomarker of mCRC, validated in the TCGA COADREAD cohort. Transcriptomic analysis revealed significant correlations between LAG3 expression and angiogenesis, epithelial–mesenchymal  \n\n| Yi-Hsuan Huang and Shang-Yin Wu have contributed equally to the work. |\n| --- |\n| Shang-Hung Chen and Yu-Min Yeh have contributed equally to the work. |\n\n* Shang-Hung Chen [bryanchen@nhri.edu.tw](bryanchen@nhri.edu.tw)  \n* Yu-Min Yeh[i5485111@gmail.com](i5485111@gmail.com)  \n1 Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n2 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n3 Division of Colorectal Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n4 Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan  \n5 National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan  \ntransition, and TGF-β signaling pathways, which were linked to immunosuppressive microenvironment and poor prognosis. Cell–cell communication analysis showed CD8⁺ T cells interact with various cell subpopulations, with Galectin-9–TIM-3 signaling uniquely present in LAG3⁺CD8⁺ T cells.  \nConclusions LAG3 expression is an independent prognostic biomarker of mCRC. The distinct Galectin-9–TIM-3 signaling in LAG3⁺CD8⁺ T cells may contribute to limited therapeutic efficacy ofLAG3 blockade, suggesting potential combinational immunotherapy strategies.  \nGraphical abstract  \nKeywords LAG3 · Metastatic colorectal cancer · TGF-β signaling pathway · TIM-3 · Tumor microenvironment  \nAbbreviations  \nCRC  \ndMMR/MSI-H  \nDSS  \nEMT  \nFFPE  \nGSEA  \nHPF  \nICI  \nIHC  \nLAG3  \nmCRCMSI-HOS  \nPFIscRNA-seq TGF-β TIL  \nTME  \nPC  \nPFIpMMR/MSS  \nColorectal cancer  \nMismatch repair–deficient/microsatellite instability–high  \nDisease-specific survival Epithelial mesenchymal transition Formalin-fixed paraffin-embedded Gene set enrichment analysis High-power field  \nImmune checkpoint inhibitors Immunohistochemistry Lymphocyte-activation gene 3  \nMe","cbCaioixQzhrCLsO","https://ap.wps.com/l/cbCaioixQzhrCLsO","pdf",3739777,15,"English","# Background\n# Methods\n# Results\n## Clinical prognostic value\n## Transcriptomic and single-cell findings\n# Conclusions\n# Graphical abstract\n# Keywords\n# Abbreviations","[{\"question\":\"What was the main aim of the study on LAG3 in metastatic colorectal cancer?\",\"answer\":\"To determine the prognostic impact of LAG3 expression in mCRC and to clarify its biological role within the mCRC immune microenvironment.\"},{\"question\":\"How was LAG3 expression measured and validated?\",\"answer\":\"LAG3 expression was assessed by immunohistochemistry in primary and/or metastatic tumors from a retrospective mCRC cohort, and prognostic findings were validated using TCGA COADREAD data.\"},{\"question\":\"What immune-related signaling was specifically linked to LAG3-positive CD8+ T cells?\",\"answer\":\"Cell–cell communication analysis highlighted Galectin-9–TIM-3 signaling as uniquely present in LAG3+ CD8+ T cells.\"}]","Clinical and immunological implications of lymphocyte-activation gene 3 expression in metastatic colorectal cancer | PDF",1790148146,38]