Self-tolerance and tumor-induced peripheral tolerance may be responsible for the limitations of the immune system in controlling tumor growth in cancer patients. It is known, that self-proteins are continuously processed and presented by antigen presenting cells. During development, auto-reactive T cells encountering self peptide/self-MHC complexes are being eliminated in the thymus. This process called 'negative selection' results in the removal of nascent auto-reactive T cells thus preventing an autoimmune attack of our own tissues. Many self-peptides (e.g. parts of p53), despite their high affinity for self-MHC, remain cryptic in the thymus and do not mediate cell deletion. Under conditions that favor up-regulation of cryptic self-determinants, one or more of these subsets of the 'protected' T cell repertoires, can be stimulated by these self-determinants, leading to induction of autoreactivity. The latter could eventually result in auto-immunity under permissive conditions governed by MHC and non-MHC genes. Thus, considering tumor tissue a 'modified self-tissue', this process that may have evolved to prevent excessive purge of the T cell repertoire, providing the potential for the development of autoimmune responses and therefore for anti-cancer therapy in adults.