{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:39:22Z","timestamp":1793209162431,"version":"4.5.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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>The interplay between malignant cells and the immunosuppressive tumor microenvironment (TME) is pivotal for lung adenocarcinoma (LUAD) progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study employed single-cell RNA sequencing, spatial transcriptomics, multi-omics analysis, and ensemble machine learning, combined with in vitro and in vivo functional experiments, to investigate the role of CCL20 in the immunosuppressive TME of LUAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a distinct, metastasis-enriched malignant epithelial subpopulation characterized by a pro-inflammatory signature and high CCL20 expression. Pseudotime and regulon analyses suggested enrichment of NF-\u03baB\/STAT signaling regulon activity during malignant evolution. Spatial transcriptomics and cellular communication inference demonstrated that CCL20-high tumor cells co-localized with and actively recruited regulatory T cells (Tregs) via the specific CCL20-CCR6 ligand-receptor pair. Multi-omics analysis confirmed that high CCL20 expression correlated with increased Treg infiltration and served as an independent prognostic biomarker. An ensemble machine learning model based on the CCL20-CCR6 axis effectively stratified high-risk patients across multiple validation datasets. Functionally, genetic ablation of CCL20 attenuated the proliferative, migratory, and invasive capacities of LUAD cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      and suppressed tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The primary causal evidence chain of this study centers on the functional validation of the CCL20-CCR6 axis in Treg chemotaxis; the upstream computational inference of NF-\u03baB\/STAT signaling regulation should be regarded as a hypothesis-generating exploration requiring further validation. CCL20 thus represents a potential prognostic biomarker and therapeutic target for LUAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1870538","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:47:39Z","timestamp":1782910059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrating multi-omics and machine learning to uncover CCL20 as a potential regulator of the immunosuppressive microenvironment in lung adenocarcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Guishi","family":"Wang","sequence":"first","affiliation":[{"name":"Henan Provincial Chest Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guichao","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Medical University","place":["Xinxiang, 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