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To replicate pathogenic processes and identify the determinants of cell evolution, a rat model is established using tobacco\u2010derived carcinogens. Here, a series of single\u2010cell transcriptome profiles of normal lung epithelium, hyperplasia, metaplasia, dysplasia, and squamous cell carcinoma in situ (CIS) to invasive squamous cell carcinoma (SCC) is presented. A large proportion of canonical copy number variations (CNVs) are detected in the hyperplasia\/metaplasia stages, with their frequency increasing as the lesion progressed. Although bronchial epithelial cells exhibit substantial heterogeneity, three distinct cellular states are identified during their evolution into malignant cells. Immune sensing occurs at the earliest stages of cellular transformation. However, persistent exposure to carcinogens induces microenvironmental remodeling, which is characterized by monocyte\u2010derived macrophage infiltration, plasmacytoid dendritic cell expansion, and progressive T\u2010cell exhaustion. These findings depict the evolutionary trajectory of cancer and the immune microenvironment, emphasizing the need for CNV evaluation in early screening and immune\u2010based therapy for lesions at a high risk of progression to LUSC.<\/jats:p>","DOI":"10.1002\/advs.202413256","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:55:16Z","timestamp":1749102916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Real\u2010Time Evolutionary Landscape of the Bronchial Epithelium and Corresponding Dynamic Immune Cell Alterations in Lung Squamous Cell Carcinogenesis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1514-2760","authenticated-orcid":false,"given":"Baohong","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong 510000 P. R. 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