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This study investigates the complex role of tumor-associated macrophages (TAMs) in the aggressive head and neck squamous cell carcinoma (HNSCC) microenvironment. Contrary to the typical protumorigenic role, functional coculture assays revealed that TAMs significantly suppressed HNSCC cell migration and invasion without affecting proliferation or apoptosis, an effect accompanied by the inhibition of epithelial-mesenchymal transition (EMT). Transcriptomic profiling identified block of proliferation 1 (BOP1) as a key gene downregulated following TAM coculture. Subsequent loss-of-function studies confirmed that silencing BOP1 alone recapitulated the suppressive effects of TAMs on cancer cell motility. Analysis of multiple independent clinical cohorts demonstrated that high BOP1 expression is significantly correlated with advanced tumor stage and worse overall survival in HNSCC patients. Importantly, elevated BOP1 levels were also associated with a reduced abundance of CD8 + T cells within the tumor microenvironment. These findings collectively unveil a tumor-restraining role for TAMs through motility and EMT inhibition, and identify BOP1 as a critical oncogenic driver that promotes HNSCC progression and is linked to impaired antitumor immunity, highlighting its dual potential as a prognostic biomarker and therapeutic target.
Mu et al. (Fri,) studied this question.