A disulfidptosis-related risk model for head and neck cancer identifying NQO1 as a key target to promote immunotherapy

Disulfidptosis has been confirmed to offer the benefit in anti-tumor immunity, yet precise prognostic models and effective immunotherapeutic targets remain limited in head and neck cancer (HNSC). This study established an HNSC-specific disulfidptosis-related risk model (HNSC-DRRM) using synthesis algorithms. Integrated single-cell and spatial transcriptomic analyses elucidated the key intercellular communication pathway within the tumor microenvironment, while patient-derived organotypic tumor spheroids and murine MOC1 xenograft models validated the therapeutic target. The HNSC-DRRM demonstrated that patients with higher prognostic risk suffered a remarkably poorer survival probability compared with their counterparts ( P < 0.001). The major pathways enriched in the low-risk group lay in adaptive immune response, antigen processing and presentation, and immune cell interactions, which were further supported by TIDE scores analysis. Additionally, the results from single-cell RNA-sequencing data described HNSC-DRRM as a multi-dimensional model integrating both tumor cells and immune cell types, and indicated CXCL12-CXCR4 as key signaling in the tumor microenvironment, which was further supported by spatial transcriptomics analysis. Finally, we identified NQO1 as a valuable therapeutic target and found that dicoumarol could enhance the anti-tumor effect of immune checkpoint therapy for HNSC. Overall, the present study manages to construct a risk model with relatively satisfactory ability related to disulfidptosis and provides a novel combination treatment strategy for HNSC patients.