A good clinical model are carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes, such as patients with Lynch syndrome (also known as Hereditary Non-Polyposis Colorectal Cancer or HNPCC). These persons have a lifetime risk of 60-80% for colorectal cancer that has developed within a few years from a precancerous adenoma. The immune system is thought to be of potential great importance as the colorectal cancer in Lynch syndrome is characterized by a strong lymphocyte infiltration, even at the stage of adenomas. In affected cancer lesions, MMR dysfunction results in frameshift mutations at short, repetitive DNA sequences referred to as microsatellites. In coding regions these mutations destroy gene function and have been demonstrated to lead to the production of neopeptides. These neopeptides are: 1) tumor specific, because frameshift mutations only occur in tumor cells and their premalignant progenitors, 2) are very similar between patients, since the same genes are affected by the mismatch repair defect and 3) immunogenic, since cytotoxic T cells (CTL) and helper T cells could be induced in vitro from blood of patients with Lynch syndrome. Similar mechanisms occur in sporadic colon cancer with MMR dysfunction, which represents about 10-15% of all colorectal 2.