Abstract. Neoantigens are tumor-specific antigens presented exclusively by cancer cells. These antigens are recognized as nonself by the host immune system

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According to the theory of immunosurveillance, the immune system can identify and eliminate cells carrying somatic mutations, thereby preventing potentially cancerous clones from expanding1. All cells display peptides generated from their proteome on their surface, allowing the immune system to detect cells that present nonself peptides. Peptide presentation requires binding to the class I major histocompatibility complex (MHC-I). The resulting peptide–MHC (p-MHC) complex is trafficked to the cell surface, where it can be recognized by CD8+ T cells2. Whether a given peptide is presented on the surface is influenced by its binding affinity to the MHC, with strongly binding peptides more likely to form the p-MHC complex3. MHC alleles are highly polymorphic in the human population4; therefore, a peptide may be differentially presented among individuals who carry different MHC alleles. It has been suggested that this may influence the expansion of driver mutations in cancer. Cancers reportedly carry driver mutations that are anomalously poor binders to the patient’s MHC5, and particular MHC alleles predicted to bind to mutant peptides with high affinity are underrepresented in some cancers6. In addition, recognition by CD8+ T cells of neoantigens presented on the MHC-II complex, which is mainly expressed in hematopoietic and immune cells7,8,...