{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:09:39Z","timestamp":1789016979043,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"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>Air pollutants are implicated in carcinogenesis, but their relevance to gastric cancer (GC) across prognosis, tumor organization and cell behavior remains unclear. We integrated evidence to evaluate pollutant-prioritized GC candidates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seven pollutants were integrated with GeneCards\/OMIM GC genes using toxicology and candidate-prioritization resources. Robustness analyses used alternative disease definitions, Fisher\u2019s tests, 5,000 degree- and annotation-matched null sets, enrichment and protein\u2013protein interaction networks. TCGA-STAD supported nested evaluation of 117 survival pipelines and a five-gene neural network, with locked external testing in GSE84437 and GSE54129. Single-cell, donor-aware macrophage, CellChat, Monocle2, multiplex immunofluorescence and cell2location-guided Visium analyses resolved tissue context. Docking, 100-ns molecular dynamics and bibliometrics examined GSK-3\u03b2-centered hypotheses. AGS cells underwent benzene\/toluene dose screening followed by CCK-8, colony formation, Transwell and wound-healing assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 176 genes, 63 overlapped with GC beyond matched-null expectations (empirical P\u2009=\u20090.012), with enrichment in inflammation, hypoxia, apoptosis, metabolism and carcinogenesis. APRGSig (DNMT1, GSK3B, HNF4A, MMP9 and TERT) remained associated with overall survival after age\/T\/N\/M adjustment (HR per 1-SD increase, 2.31; 95% CI, 1.98\u20132.71) and achieved a locked external C-index of 0.701; exploratory GC-ANN achieved an external AUC of 0.962. Score-defined APRGSig-high macrophages showed broader predicted crosstalk, whereas donor-aware analysis identified an inflammatory\/stress-associated MALAT1-high state. Multiplex immunofluorescence provided representative compartment-level localization of APRGSig-encoded proteins; four Visium sections showed directionally consistent positive spatial concordance between APRGSig scores and inferred MALAT1-high abundance. Formal GSK-3\u03b2\u2013benzene\/toluene models yielded Vina scores of \u22127.1\/\u22127.4\u2009kcal\/mol and remained numerically persistent over 100 ns; bibliometrics of 311 publications highlighted proliferation, invasion and metastasis. At 2.5\u2009mM benzene and 20\u2009\u03bcM toluene, both exposures increased AGS clonogenic capacity, Matrigel traversal and wound closure (all P\u2009&amp;lt;\u20090.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This framework integrates predictive, tissue-resolved, structural and phenotype-level evidence to prioritize exposure-linked molecular and immune hypotheses in GC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1951968","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:29:18Z","timestamp":1789014558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiscale characterization of an inflammatory macrophage state associated with an air pollutant\u2013prioritized prognostic signature in gastric cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Luming","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People\u2019s Hospital of Lianyungang","place":["Lianyungang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Lianyungang Clinical College of Nanjing Medical University\/The First People's Hospital of Lianyungang","place":["Lianyungang, 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