{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:41:48Z","timestamp":1792503708706,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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>Objective<\/jats:title>\n                    <jats:p>Pulmonary nodules (PN) represent a clinically heterogeneous pathway that includes benign lesions, adenocarcinoma-spectrum lesions, and cases that may differ from clinically overt lung cancer (LC). This study aimed to define a peripheral blood immunophenotyping framework for this pathway by integrating routine inflammatory readouts with transparently defined whole-blood flow-cytometry immune modules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective analysis of a single-center locked cohort of 217 participants, including healthy controls (n=121), pulmonary nodules (n=46), and overt lung cancer (n=50). The PN group was further stratified into benign PN (n=20) and adenocarcinoma-spectrum PN (n=26). Clinical readouts included neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), albumin, and lymphocyte measures. Peripheral immune phenotypes were summarized using four code-defined flow-cytometry module scores: B-cell remodeling, Tfh\/Th2 skew, cytotoxic attenuation, and CD28-loss. Group differences were evaluated using Cliff\u2019s delta with 95% confidence intervals and FDR-adjusted q values, with adjusted models used only as supportive diagnostics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Within the PN cohort, adenocarcinoma-spectrum PN showed a coherent inflammatory and lymphocyte-axis shift relative to benign PN, including higher NLR (delta=0.70, q&amp;lt;0.001), higher SII (delta=0.62, q&amp;lt;0.001), higher inflammation score (delta=0.81, q&amp;lt;0.001), lower albumin (delta=-0.69, q&amp;lt;0.001), and lower lymphocyte percentage (delta=-0.72, q&amp;lt;0.001). In the peripheral immune layer, overt LC showed higher module scores than PN across B-cell remodeling (delta=0.38, q=0.002), Tfh\/Th2 skew (delta=0.40, q=0.001), cytotoxic attenuation (delta=0.47, q&amp;lt;0.001), and CD28-loss (delta=0.27, q=0.021). Focused and sensitivity comparisons preserved the direction of the module findings, with the strongest support for cytotoxic attenuation and Tfh\/Th2 skew.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a clinically anchored description of peripheral inflammatory and immune patterns across clinically defined PN and overt LC groups. The findings identify inflammatory heterogeneity within PN and higher immune-module scores in overt LC, providing a hypothesis-generating framework for prospective validation and paired tissue-peripheral studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1920402","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:27:03Z","timestamp":1788236823000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical inflammatory shifts and peripheral flow-cytometry immune modules across benign pulmonary nodules, adenocarcinoma-spectrum nodules, and overt lung cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Yunwei","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, 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