Head and neck squamous cell carcinoma (HNSC) represents nearly 90% of all head and neck tumors. The current treatment modality for HNSC patients primarily involves surgical intervention and radiotherapy, but its therapeutic efficacy remains limited. The mRNA vaccine based on tumor antigens seems promising for cancer treatment. Ferroptosis, a novel form of cell death, is linked to tumor progression and cancer immunotherapy. Nevertheless, the effectiveness of ferroptosis-associated tumor antigens in treating HNSC remains uncertain. In this study, we identified three ferroptosis-associated tumor antigens, namely caveolin1 (CAV1), ferritin heavy chain (FTH1), and solute carrier 3A2 (SLC3A2), as being overexpressed and mutated based on data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. These antigens were strongly associated with poor prognosis and infiltration of antigen-presenting cells in HNSC. We further identified two ferroptosis subtypes (FS1 and FS2) with distinct molecular, cellular, and clinical properties to identify antigen-sensitive individuals. Our findings indicate that FS1 exhibits an immune "hot" phenotype, whereas FS2 displays an immune "cold" phenotype. Additionally, differential expression of immunogenic cell death modulators and immune checkpoints was observed between these two immune subtypes. Further exploration of the HNSC's immune landscape revealed significant heterogeneity among individual patients. Our findings suggest that CAV1, FTH1, and SLC3A2 are potential targets to prevent HNSC in FS2 patients. Overall, our research reveals the potential of ferroptosis-associated mRNA vaccines for HNSC and identifies an effective patient population for vaccine treatment.

头颈鳞状细胞癌 (HNSC) 占所有头颈肿瘤的近 90%。目前HNSC患者的治疗方式主要包括手术干预和放射治疗，但其治疗效果仍然有限。基于肿瘤抗原的 mRNA 疫苗似乎有望用于癌症治疗。铁死亡是一种新型的细胞死亡形式，与肿瘤进展和癌症免疫治疗有关。然而，铁死亡相关肿瘤抗原治疗 HNSC 的有效性仍不确定。在这项研究中，我们根据从癌症基因组图谱和基因中获得的数据，确定了三种与铁死亡相关的肿瘤抗原，即小窝蛋白1（CAV1）、铁蛋白重链（FTH1）和溶质载体3A2（SLC3A2），它们被过度表达和突变。表达式综合数据库。这些抗原与 HNSC 中的不良预后和抗原呈递细胞浸润密切相关。我们进一步鉴定了两种具有不同分子、细胞和临床特性的铁死亡亚型（FS1 和 FS2），以识别抗原敏感个体。我们的研究结果表明，FS1 表现出免疫“热”表型，而 FS2 表现出免疫“冷”表型。此外，在这两种免疫亚型之间观察到免疫原性细胞死亡调节剂和免疫检查点的差异表达。对 HNSC 免疫状况的进一步探索揭示了个体患者之间的显着异质性。我们的研究结果表明，CAV1、FTH1 和 SLC3A2 是预防 FS2 患者 HNSC 的潜在靶点。总体而言，我们的研究揭示了铁死亡相关 mRNA 疫苗治疗 HNSC 的潜力，并确定了疫苗治疗的有效患者群体。