A single-cell atlas reveals the tumorigenesis and microenvironment status of primary tracheobronchial tumors

Primary tracheobronchial tumors (PTBTs) can often be successfully treated by surgery; however, more effective strategies are still warranted for advance tumor cases. The present study aimed to provide a comprehensive understanding of the molecular and cellular features of PTBTs, along with the tumor microenvironment (TME). By performing single-cell RNA, we revealed a distinct TME landscape of PTBTs containing 52,739 single cells. For instance, these three pathological types were found have heterogeneous fibroblast populations, immune cells were more activated in inflammatory myofibroblastic tumor (IMT). Notably, a subpopulation of BIRC5⁺ cells was identified in primary tracheal squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) samples, which may have similar properties to cancer stem cells (CSCs). Moreover, IMT was characterized by the infiltration of pro-inflammatory immune cells, and might be a benign tumor. Importantly, based on ligand-receptor analysis, the PPIA/CD147 pair was found to be strongly upregulated during tumor and CD8⁺ T cell interactions. By applying multiplex immunofluorescence for selected markers, we validated the presence of the separate cell entities. Our findings provide deeper insights into the biology of PTBTs, which may be beneficial for advancing the diagnosis and therapy of PTBTs.