A gene expression-based immune content predictor for survival and postoperative radiotherapy response in head and neck cancer

The immune infiltration in the tumor microenvironment has been demonstrated to be relevant to radiotherapy response. Here, we sought to understand the immune infiltration in head and neck cancer (HNC) and evaluate its significance in predicting prognosis and radiotherapy response. Using RNA sequencing data of 522 retrospective head and neck squamous cell carcinomas (HNSCCs), we constructed an immune content score based on genes related to 6 prognostic infiltrating cell types. Unsupervised hallmark pathway clustering demonstrated an immune-related tumor cluster containing the immune content score. Patients with high immune content scores exhibited favorable overall survival and disease-free survival (DFS). Moreover, the immune content score was an independent prognostic factor for DFS in HNSCC. Interestingly, the immune content score was strongly associated with radiation response pathways. These results were also extended to nasopharyngeal carcinoma. Furthermore, patients in the low immune content score group significantly gained overall survival benefits from postoperative radiotherapy (PORT), whereas patients in the high immune content score group did not. Therefore, this study identifies the immune content score as a prognostic tool, which might have a potential association with PORT response, thereby facilitating outcome prediction and treatment decision in HNC.