Although tumor immunotherapy benefits from high loads of tumor-specific mutations and high frequencies of neoantigen-specific CTLs7,9,55–57, natural neoantigen-specific CD8+ CTLs are often rare (e.g., 0.002–0.4% in melanoma, which already has the second highest tumor mutation loads58,59), likely due to low clonal neoantigen burden, inefficient antigen processing and cross presentation, and immunosuppression. This evidence concerns the gene CD8A and neoplasm.