While it is difficult to determine the frequency of antigen-specific CD4 T cells because of the lack of reliable method such as tetramer staining to detect these few CD4 T cells, we described that HER-3 reactive CD4 T cells existed in HNSCC patients indicating the immunogenicity of HER-3 in HNSCC patients (Fig. 7). This evidence concerns the gene ERBB3 and head and neck squamous cell carcinoma.