Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a multisite malignancy that responds well to immunotherapy. Despite the initial enthusiasm, the clinical benefits of immunotherapy in HNSCC patients are overall limited. Endoplasmic reticulum stress (ERS) has been indicated to play a key role in the process of anti-tumor immune response mediation. However, ERS-related biomarkers which can accurately predict prognosis and immunotherapy response in HNSCC are still lacking. METHODS AND RESULTS: In this study, we identify and validate an ERS-related signature comprises of six genes (ASNS, EXOSC6, BAK1, TPP1, EXOSC8, and TATDN2) that can predict the prognosis of HNSCC patients. GSEA analysis indicates that the ERS-related signature is significantly correlated with tumor immunity in HNSCC. Moreover, the infiltration of naive B cells and CD8 + T cells are significantly diminished in patients with high-risk scores compared to those with low-risk scores, while macrophages and activated mast cells are remarkably enhanced. Furthermore, the ERS-related signature also displays a tremendous potential for predicting immunotherapy response in HNSCC. CONCLUSIONS: Our study identifies an ERS-related signature that can predict the prognosis of HNSCC patients and highlights its potential value as a predictive biomarker of immunotherapy response, potentially enabling more precise and personalized immunotherapy response and paving the way for further investigation of the prognostic and therapeutic potentials of ERS.