How patients with an intact immune system develop head and neck cancer

Although the adaptive immune system can detect and eliminate malignant cells, patients with intact and fully functional immune systems develop head and neck cancer. How is this paradox explained? Manuscripts published in the English language from 1975 to 2018 were reviewed using search inputs related to tumor cell antigenicity and immunogenicity, immunodominance, cancer immunoediting and genomic alterations present within carcinomas. Early in tumor development, T cell responses to immunodominant antigens may lead to the elimination of cancer cells expressing these antigens and a tumor composed to tumor cells expressing only immunorecessive antigens. Conversely, other tumor cells may acquire genomic or epigenetic alterations that result in an antigen processing or presentation defect or other inability to be detected or killed by T cells. Such T cell insensitive tumor cells may also be selected for in a progressing tumor. Tumors harboring subpopulations of cells that cannot be eliminated by T cells may require non-T cell-based treatments, such as NK cell immunotherapies. Recognition of such tumor cell populations within a heterogeneous cancer may inform the selection of treatment for HNSCC in the future.