Immunotherapy involving CTL is an attractive alternative for treatment of various malignancies. One of the approaches currently being explored for immune targeting of human cancers involves potentiation of immunogenicity of malignant cells by gene transduction. This strategy is undoubtedly influenced by the ability of the malignant cells to endogenously process and present target epitopes on their cell surface for immune recognition by CTL. However, there is increasing evidence to suggest that a large proportion of human cancers escape CTL-mediated immune surveillance by selectively down-regulating the expression of MHC class I molecules and peptide transporter genes. Understanding and molecular analysis of these immunologically relevant genetic defects in tumours is very important before translating preclinical studies of immunotherapy to rational clinical trials. Careful consideration of these potential limitations may lead to the development of novel immunotherapeutic strategies and, potentially, prevention of tumour progression or development.