Catechin suppresses HNSC via STXBP1 dependent inhibition of macrophage infiltration and CD47 mediated immune evasion

The treatment of head and neck squamous cell carcinoma (HNSC) faces significant challenges, primarily due to the lack of reliable biomarkers and effective therapeutic drugs. This study reveals the crucial mechanistic role of STXBP1 in the HNSC tumor microenvironment: STXBP1 promotes tumor immune escape through dual pathways, not only enhancing the infiltration of M2-type macrophages but also activating the 'don't eat me' signaling pathway through upregulation of CD47. Clinical data analysis demonstrates that STXBP1 expression levels significantly correlate with HNSC patient prognosis, suggesting its potential as a diagnostic marker and prognostic indicator. Mechanistic studies show that targeted inhibition of STXBP1 effectively downregulates CD47 expression and restores the anti-tumor function of macrophages. Based on bioinformatics screening and experimental validation, we discovered that the natural compound Catechin can specifically inhibit STXBP1 expression and significantly suppress tumor growth. These findings not only elucidate the molecular mechanism of STXBP1 in HNSC but also provide a new candidate drug for clinical treatment, holding significant translational medical value.