This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.

External beam radiotherapy is a major treatment in the management of cancer .However radia-tion induced pulmonary fibrosis is common .It not only leads to quality -of-life issues in survivors and compro-mise treatment ,but also may even be lethal in outcome .Transforming growth factor β( TGF-β) seems to be a key mediator of fibrosis .TGF-βpromotes the differentiation of fibroblasts into myofibroblasts while the differentiation and activation of fibroblasts and myofibroblastsmay produce the components of scar tissue, which is one of the key pathogenic processes in lung fibrosis .Peroxisome proliferator activated receptors ( PPARs ) are ligand activated transcription factors that belong to the nuclear hormone receptor superfamily .PPARγis also a key regulator of fi-broblast differentiation .Many studies have shown that both natural ligand and synthetic ligand of PPARγcan sup-press fibrosis by interfering with TGF -βsignaling and some other approaches .The antifibrotic effects of PPARγhave been reported to be involved in both PPARγdependent and PPARγindependent mechanisms .PPARγago-nists may have potential for the therapy of radiation induced pulmonary fibrosis .