{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:17Z","timestamp":1787120837612,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Predicting occult lymph node metastasis in early-stage tongue squamous cell carcinoma remains a clinical challenge because traditional markers, such as depth of invasion, exhibit limited accuracy. This study aimed to identify spatial immunological biomarkers to improve risk stratification and clinical decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Olink proteomic profiling was conducted to screen for metastasis-associated biomarkers. Subsequently, multiplex immunofluorescence coupled with artificial intelligence-powered spatial analysis was utilized to evaluate the microenvironment in primary lesions and paired cervical lymph nodes. A novel \u201cSpatial Availability Index\u201d was applied to map cellular distribution, and diagnostic performance was evaluated using receiver operating characteristic curve analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Arginase-1 (ARG1) was identified as a top candidate biomarker, exhibiting a unique \u201ctissue-low, serum-high\u201d expression pattern in cases with occult metastasis. Spatial analysis revealed a significant depletion of ARG1\n                      <jats:sup>+<\/jats:sup>\n                      polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in both primary tumors and paired lymph nodes during metastatic progression. Specifically, the reduction of these intact cells was most pronounced within a 35-\u03bcm proximal segment from the tumor boundary. This localized cellular loss inversely correlated with an accumulation of neutrophil extracellular traps (NETs) at the peritumoral interface, indicating that ARG1\n                      <jats:sup>+<\/jats:sup>\n                      PMN-MDSC-associated spatial alterations coincide with NET-associated remodeling at the peritumoral interface. Integrating the intrastromal density of ARG1\n                      <jats:sup>+<\/jats:sup>\n                      PMN-MDSCs with depth of invasion significantly enhanced the diagnostic accuracy for occult metastasis (Area Under the Curve = 0.8318) compared to using depth of invasion alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Early metastatic risk is driven by localized alterations within the myeloid compartment, characterized by the transition of intact ARG1\n                      <jats:sup>+<\/jats:sup>\n                      PMN-MDSCs to NETs within a 35-\u03bcm peritumoral hotspot. This spatial biomarker provides a high-resolution tool to optimize patient selection for elective neck dissection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1910935","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:44:59Z","timestamp":1787118299000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The spatial landscape of the peritumoral interface: ARG1+ PMN-MDSCs reduction and NETosis as indicators of occult metastasis in tongue squamous cell carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Shengqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology","place":["Beijing, China"]},{"name":"Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology","place":["Beijing, China"]},{"name":"Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials","place":["Beijing, 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School and Hospital of Stomatology","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diancan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology","place":["Beijing, China"]},{"name":"Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Hebei Medical University, Hebei Technology Innovation 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