头颈部鳞状细胞癌（HNSCC）是一种多部位恶性肿瘤，对免疫疗法有很好的反应。尽管最初充满热情，但免疫疗法在HNSCC患者中的临床益处总体上有限。内质网应激（ERS）被认为在抗肿瘤免疫应答调节过程中发挥关键作用。然而，在HNSCC中缺乏能够准确预测预后和免疫疗法反应的ERS相关生物标志物。在本研究中，我们确定并验证了一个由六个基因（ASNS、EXOSC6、BAK1、TPP1、EXOSC8和TATDN2）组成的ERS相关标志，可预测HNSCC患者的预后。GSEA分析表明，ERS相关签名与HNSCC肿瘤免疫显着相关。此外，高危分数患者的未成熟B细胞和CD8 + T细胞浸润明显减少，而巨噬细胞和活化肥大细胞显著增强。此外，ERS相关签名还显示出巨大的预测HNSCC免疫疗法反应的潜力。我们的研究确定了一个ERS相关标记，可预测HNSCC患者的预后，并强调了其作为免疫疗法反应预测生物标志物的潜在价值，可能实现更精确、个性化的免疫疗法反应，为ERS的预后和治疗潜力的进一步研究铺平道路。© 2023年作者。

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.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.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.© 2023. The Author(s).