{"title":"Spatial transcriptomics reveals immune remodeling in lymph nodes of gastric adenocarcinoma.","authors":"Thanawat Suwatthanarak, Chawisa Nampoolsuksan, Pariyada Tanjak, Kullanist Thanormjit, Onchira Acharayothin, Amphun Chaiboonchoe, Tharathorn Suwatthanarak, Manop Pithukpakorn, Wipapat Vicki Chalermwai, Jirawat Swangsri, Asada Methasate, Vitoon Chinswangwatanakul, Thammawat Parakonthun","doi":"10.1007/s10585-026-10429-7","DOIUrl":null,"url":null,"abstract":"<p><p>Lymph node (LN) metastasis is a major determinant of prognosis in gastric cancer, yet the immune microenvironment of metastatic versus non-metastatic nodes remains incompletely defined. Spatial resolution of tumor-immune interactions may clarify mechanisms of immune escape associated with nodal progression. We performed compartment-resolved spatial transcriptomic profiling to characterize immune gene expression in gastric cancer LNs. Forty-seven formalin-fixed paraffin-embedded LNs from 13 patients with T2-T4, M0 gastric adenocarcinoma (N1-2: n = 7; N3: n = 6) were analyzed using the NanoString GeoMx Digital Spatial Profiler and an 84-gene immune pathways panel. Twenty-nine non-metastatic and 18 metastatic LNs were profiled. Regions of interest were segmented into tumor and immune compartments, yielding 65 spatially defined compartments. Differential expression was assessed across three comparisons: metastatic versus non-metastatic LNs; metastatic LNs from N1-2 versus N3 patients; and non-metastatic LNs from N1-2 versus N3 patients. Within the immune compartments, non-metastatic LNs showed higher expression of T-cell activation and checkpoint genes (CD3E, CD27, PDCD1, CTLA4), consistent with preserved immune surveillance. Metastatic LNs were enriched for WNT signaling and adhesion-related genes (CTNNB1, ITGAV) and epithelial markers (EPCAM), indicating tumor-driven immune remodeling. N3 metastatic LNs demonstrated increased ICOSLG, IL6, and IFNGR1 expression, suggesting chronic inflammatory activation and immune dysfunction. Notably, non-metastatic LNs from N3 patients upregulated antigen-presentation genes (CD74, HLA-DRB), consistent with early immune conditioning. No significant differences emerged in tumor compartments or pseudo-bulk analyses. Spatial transcriptomic profiling reveals nodal burden-associated immune remodeling, and identifies candidate biomarkers and therapeutic targets for precision immunotherapy in gastric cancer.</p>","PeriodicalId":10267,"journal":{"name":"Clinical & Experimental Metastasis","volume":"43 5","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585797/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Experimental Metastasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10585-026-10429-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Lymph node (LN) metastasis is a major determinant of prognosis in gastric cancer, yet the immune microenvironment of metastatic versus non-metastatic nodes remains incompletely defined. Spatial resolution of tumor-immune interactions may clarify mechanisms of immune escape associated with nodal progression. We performed compartment-resolved spatial transcriptomic profiling to characterize immune gene expression in gastric cancer LNs. Forty-seven formalin-fixed paraffin-embedded LNs from 13 patients with T2-T4, M0 gastric adenocarcinoma (N1-2: n = 7; N3: n = 6) were analyzed using the NanoString GeoMx Digital Spatial Profiler and an 84-gene immune pathways panel. Twenty-nine non-metastatic and 18 metastatic LNs were profiled. Regions of interest were segmented into tumor and immune compartments, yielding 65 spatially defined compartments. Differential expression was assessed across three comparisons: metastatic versus non-metastatic LNs; metastatic LNs from N1-2 versus N3 patients; and non-metastatic LNs from N1-2 versus N3 patients. Within the immune compartments, non-metastatic LNs showed higher expression of T-cell activation and checkpoint genes (CD3E, CD27, PDCD1, CTLA4), consistent with preserved immune surveillance. Metastatic LNs were enriched for WNT signaling and adhesion-related genes (CTNNB1, ITGAV) and epithelial markers (EPCAM), indicating tumor-driven immune remodeling. N3 metastatic LNs demonstrated increased ICOSLG, IL6, and IFNGR1 expression, suggesting chronic inflammatory activation and immune dysfunction. Notably, non-metastatic LNs from N3 patients upregulated antigen-presentation genes (CD74, HLA-DRB), consistent with early immune conditioning. No significant differences emerged in tumor compartments or pseudo-bulk analyses. Spatial transcriptomic profiling reveals nodal burden-associated immune remodeling, and identifies candidate biomarkers and therapeutic targets for precision immunotherapy in gastric cancer.
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The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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