Despite the wide variety of immunotherapy‐based approaches, most of these methods, such as checkpoint blockers, have not successfully treated CRC.[14] Accordingly, some rare studies explored the practicability and usefulness of neoantigens‐based immunotherapy in treating CRC.[83, 84, 85] A study of CRC subsets showed the importance of mutations in genes that are involved in DNA repairs, such as MLH1, MSH2, MSH6, POLE, EXO1, and MUTYH, because these alterations can lead to the formation of neoantigens and disruption of antigen presentation to effector T cells in CRC. This evidence concerns the gene POLE and colorectal carcinoma.